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Stem Cell Research Benefits

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Introduction:, conclusion:, 1. treating diseases:, 2. personalized medicine:, 3. drug development and testing:, 4. understanding development and disease:.

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Published: 26 February 2019

Stem cells: past, present, and future

Wojciech Zakrzewski 1 ,
Maciej Dobrzyński 2 ,
Maria Szymonowicz 1 &
Zbigniew Rybak 1

Stem Cell Research & Therapy volume 10 , Article number: 68 ( 2019 ) Cite this article

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In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great expectations. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. The genesis of stem cells is followed by laboratory steps of controlled stem cell culturing and derivation. Quality control and teratoma formation assays are important procedures in assessing the properties of the stem cells tested. Derivation methods and the utilization of culturing media are crucial to set proper environmental conditions for controlled differentiation. Among many types of stem tissue applications, the use of graphene scaffolds and the potential of extracellular vesicle-based therapies require attention due to their versatility. The review is summarized by challenges that stem cell therapy must overcome to be accepted worldwide. A wide variety of possibilities makes this cutting edge therapy a turning point in modern medicine, providing hope for untreatable diseases.

Stem cell classification

Stem cells are unspecialized cells of the human body. They are able to differentiate into any cell of an organism and have the ability of self-renewal. Stem cells exist both in embryos and adult cells. There are several steps of specialization. Developmental potency is reduced with each step, which means that a unipotent stem cell is not able to differentiate into as many types of cells as a pluripotent one. This chapter will focus on stem cell classification to make it easier for the reader to comprehend the following chapters.

Totipotent stem cells are able to divide and differentiate into cells of the whole organism. Totipotency has the highest differentiation potential and allows cells to form both embryo and extra-embryonic structures. One example of a totipotent cell is a zygote, which is formed after a sperm fertilizes an egg. These cells can later develop either into any of the three germ layers or form a placenta. After approximately 4 days, the blastocyst’s inner cell mass becomes pluripotent. This structure is the source of pluripotent cells.

Pluripotent stem cells (PSCs) form cells of all germ layers but not extraembryonic structures, such as the placenta. Embryonic stem cells (ESCs) are an example. ESCs are derived from the inner cell mass of preimplantation embryos. Another example is induced pluripotent stem cells (iPSCs) derived from the epiblast layer of implanted embryos. Their pluripotency is a continuum, starting from completely pluripotent cells such as ESCs and iPSCs and ending on representatives with less potency—multi-, oligo- or unipotent cells. One of the methods to assess their activity and spectrum is the teratoma formation assay. iPSCs are artificially generated from somatic cells, and they function similarly to PSCs. Their culturing and utilization are very promising for present and future regenerative medicine.

Multipotent stem cells have a narrower spectrum of differentiation than PSCs, but they can specialize in discrete cells of specific cell lineages. One example is a haematopoietic stem cell, which can develop into several types of blood cells. After differentiation, a haematopoietic stem cell becomes an oligopotent cell. Its differentiation abilities are then restricted to cells of its lineage. However, some multipotent cells are capable of conversion into unrelated cell types, which suggests naming them pluripotent cells.

Oligopotent stem cells can differentiate into several cell types. A myeloid stem cell is an example that can divide into white blood cells but not red blood cells.

Unipotent stem cells are characterized by the narrowest differentiation capabilities and a special property of dividing repeatedly. Their latter feature makes them a promising candidate for therapeutic use in regenerative medicine. These cells are only able to form one cell type, e.g. dermatocytes.

Stem cell biology

A blastocyst is formed after the fusion of sperm and ovum fertilization. Its inner wall is lined with short-lived stem cells, namely, embryonic stem cells. Blastocysts are composed of two distinct cell types: the inner cell mass (ICM), which develops into epiblasts and induces the development of a foetus, and the trophectoderm (TE). Blastocysts are responsible for the regulation of the ICM microenvironment. The TE continues to develop and forms the extraembryonic support structures needed for the successful origin of the embryo, such as the placenta. As the TE begins to form a specialized support structure, the ICM cells remain undifferentiated, fully pluripotent and proliferative [ 1 ]. The pluripotency of stem cells allows them to form any cell of the organism. Human embryonic stem cells (hESCs) are derived from the ICM. During the process of embryogenesis, cells form aggregations called germ layers: endoderm, mesoderm and ectoderm (Fig. 1 ), each eventually giving rise to differentiated cells and tissues of the foetus and, later on, the adult organism [ 2 ]. After hESCs differentiate into one of the germ layers, they become multipotent stem cells, whose potency is limited to only the cells of the germ layer. This process is short in human development. After that, pluripotent stem cells occur all over the organism as undifferentiated cells, and their key abilities are proliferation by the formation of the next generation of stem cells and differentiation into specialized cells under certain physiological conditions.

Oocyte development and formation of stem cells: the blastocoel, which is formed from oocytes, consists of embryonic stem cells that later differentiate into mesodermal, ectodermal, or endodermal cells. Blastocoel develops into the gastrula

Signals that influence the stem cell specialization process can be divided into external, such as physical contact between cells or chemical secretion by surrounding tissue, and internal, which are signals controlled by genes in DNA.

Stem cells also act as internal repair systems of the body. The replenishment and formation of new cells are unlimited as long as an organism is alive. Stem cell activity depends on the organ in which they are in; for example, in bone marrow, their division is constant, although in organs such as the pancreas, division only occurs under special physiological conditions.

Stem cell functional division

Whole-body development.

During division, the presence of different stem cells depends on organism development. Somatic stem cell ESCs can be distinguished. Although the derivation of ESCs without separation from the TE is possible, such a combination has growth limits. Because proliferating actions are limited, co-culture of these is usually avoided.

ESCs are derived from the inner cell mass of the blastocyst, which is a stage of pre-implantation embryo ca. 4 days after fertilization. After that, these cells are placed in a culture dish filled with culture medium. Passage is an inefficient but popular process of sub-culturing cells to other dishes. These cells can be described as pluripotent because they are able to eventually differentiate into every cell type in the organism. Since the beginning of their studies, there have been ethical restrictions connected to the medical use of ESCs in therapies. Most embryonic stem cells are developed from eggs that have been fertilized in an in vitro clinic, not from eggs fertilized in vivo.

Somatic or adult stem cells are undifferentiated and found among differentiated cells in the whole body after development. The function of these cells is to enable the healing, growth, and replacement of cells that are lost each day. These cells have a restricted range of differentiation options. Among many types, there are the following:

Mesenchymal stem cells are present in many tissues. In bone marrow, these cells differentiate mainly into the bone, cartilage, and fat cells. As stem cells, they are an exception because they act pluripotently and can specialize in the cells of any germ layer.

Neural cells give rise to nerve cells and their supporting cells—oligodendrocytes and astrocytes.

Haematopoietic stem cells form all kinds of blood cells: red, white, and platelets.

Skin stem cells form, for example, keratinocytes, which form a protective layer of skin.

The proliferation time of somatic stem cells is longer than that of ESCs. It is possible to reprogram adult stem cells back to their pluripotent state. This can be performed by transferring the adult nucleus into the cytoplasm of an oocyte or by fusion with the pluripotent cell. The same technique was used during cloning of the famous Dolly sheep.

hESCs are involved in whole-body development. They can differentiate into pluripotent, totipotent, multipotent, and unipotent cells (Fig. 2 ) [ 2 ].

Changes in the potency of stem cells in human body development. Potency ranges from pluripotent cells of the blastocyst to unipotent cells of a specific tissue in a human body such as the skin, CNS, or bone marrow. Reversed pluripotency can be achieved by the formation of induced pluripotent stem cells using either octamer-binding transcription factor (Oct4), sex-determining region Y (Sox2), Kruppel-like factor 4 (Klf4), or the Myc gene

Pluripotent cells can be named totipotent if they can additionally form extraembryonic tissues of the embryo. Multipotent cells are restricted in differentiating to each cell type of given tissue. When tissue contains only one lineage of cells, stem cells that form them are called either called oligo- or unipotent.

iPSC quality control and recognition by morphological differences

The comparability of stem cell lines from different individuals is needed for iPSC lines to be used in therapeutics [ 3 ]. Among critical quality procedures, the following can be distinguished:

Short tandem repeat analysis—This is the comparison of specific loci on the DNA of the samples. It is used in measuring an exact number of repeating units. One unit consists of 2 to 13 nucleotides repeating many times on the DNA strand. A polymerase chain reaction is used to check the lengths of short tandem repeats. The genotyping procedure of source tissue, cells, and iPSC seed and master cell banks is recommended.

Identity analysis—The unintentional switching of lines, resulting in other stem cell line contamination, requires rigorous assay for cell line identification.

Residual vector testing—An appearance of reprogramming vectors integrated into the host genome is hazardous, and testing their presence is a mandatory procedure. It is a commonly used procedure for generating high-quality iPSC lines. An acceptable threshold in high-quality research-grade iPSC line collections is ≤ 1 plasmid copies per 100 cells. During the procedure, 2 different regions, common to all plasmids, should be used as specific targets, such as EBNA and CAG sequences [ 3 ]. To accurately represent the test reactions, a standard curve needs to be prepared in a carrier of gDNA from a well-characterized hPSC line. For calculations of plasmid copies per cell, it is crucial to incorporate internal reference gDNA sequences to allow the quantification of, for example, ribonuclease P (RNaseP) or human telomerase reverse transcriptase (hTERT).

Karyotype—A long-term culture of hESCs can accumulate culture-driven mutations [ 4 ]. Because of that, it is crucial to pay additional attention to genomic integrity. Karyotype tests can be performed by resuscitating representative aliquots and culturing them for 48–72 h before harvesting cells for karyotypic analysis. If abnormalities are found within the first 20 karyotypes, the analysis must be repeated on a fresh sample. When this situation is repeated, the line is evaluated as abnormal. Repeated abnormalities must be recorded. Although karyology is a crucial procedure in stem cell quality control, the single nucleotide polymorphism (SNP) array, discussed later, has approximately 50 times higher resolution.

Viral testing—When assessing the quality of stem cells, all tests for harmful human adventitious agents must be performed (e.g. hepatitis C or human immunodeficiency virus). This procedure must be performed in the case of non-xeno-free culture agents.

Bacteriology—Bacterial or fungal sterility tests can be divided into culture- or broth-based tests. All the procedures must be recommended by pharmacopoeia for the jurisdiction in which the work is performed.

Single nucleotide polymorphism arrays—This procedure is a type of DNA microarray that detects population polymorphisms by enabling the detection of subchromosomal changes and the copy-neutral loss of heterozygosity, as well as an indication of cellular transformation. The SNP assay consists of three components. The first is labelling fragmented nucleic acid sequences with fluorescent dyes. The second is an array that contains immobilized allele-specific oligonucleotide (ASO) probes. The last component detects, records, and eventually interprets the signal.

Flow cytometry—This is a technique that utilizes light to count and profile cells in a heterogeneous fluid mixture. It allows researchers to accurately and rapidly collect data from heterogeneous fluid mixtures with live cells. Cells are passed through a narrow channel one by one. During light illumination, sensors detect light emitted or refracted from the cells. The last step is data analysis, compilation and integration into a comprehensive picture of the sample.

Phenotypic pluripotency assays—Recognizing undifferentiated cells is crucial in successful stem cell therapy. Among other characteristics, stem cells appear to have a distinct morphology with a high nucleus to cytoplasm ratio and a prominent nucleolus. Cells appear to be flat with defined borders, in contrast to differentiating colonies, which appear as loosely located cells with rough borders [ 5 ]. It is important that images of ideal and poor quality colonies for each cell line are kept in laboratories, so whenever there is doubt about the quality of culture, it can always be checked according to the representative image. Embryoid body formation or directed differentiation of monolayer cultures to produce cell types representative of all three embryonic germ layers must be performed. It is important to note that colonies cultured under different conditions may have different morphologies [ 6 ].

Histone modification and DNA methylation—Quality control can be achieved by using epigenetic analysis tools such as histone modification or DNA methylation. When stem cells differentiate, the methylation process silences pluripotency genes, which reduces differentiation potential, although other genes may undergo demethylation to become expressed [ 7 ]. It is important to emphasize that stem cell identity, together with its morphological characteristics, is also related to its epigenetic profile [ 8 , 9 ]. According to Brindley [ 10 ], there is a relationship between epigenetic changes, pluripotency, and cell expansion conditions, which emphasizes that unmethylated regions appear to be serum-dependent.

hESC derivation and media

hESCs can be derived using a variety of methods, from classic culturing to laser-assisted methodologies or microsurgery [ 11 ]. hESC differentiation must be specified to avoid teratoma formation (see Fig. 3 ).

Spontaneous differentiation of hESCs causes the formation of a heterogeneous cell population. There is a different result, however, when commitment signals (in forms of soluble factors and culture conditions) are applied and enable the selection of progenitor cells

hESCs spontaneously differentiate into embryonic bodies (EBs) [ 12 ]. EBs can be studied instead of embryos or animals to predict their effects on early human development. There are many different methods for acquiring EBs, such as bioreactor culture [ 13 ], hanging drop culture [ 12 ], or microwell technology [ 14 , 15 ]. These methods allow specific precursors to form in vitro [ 16 ].

The essential part of these culturing procedures is a separation of inner cell mass to culture future hESCs (Fig. 4 ) [ 17 ]. Rosowski et al. [ 18 ] emphasizes that particular attention must be taken in controlling spontaneous differentiation. When the colony reaches the appropriate size, cells must be separated. The occurrence of pluripotent cells lasts for 1–2 days. Because the classical utilization of hESCs caused ethical concerns about gastrulas used during procedures, Chung et al. [ 19 ] found out that it is also possible to obtain hESCs from four cell embryos, leaving a higher probability of embryo survival. Additionally, Zhang et al. [ 20 ] used only in vitro fertilization growth-arrested cells.

Culturing of pluripotent stem cells in vitro. Three days after fertilization, totipotent cells are formed. Blastocysts with ICM are formed on the sixth day after fertilization. Pluripotent stem cells from ICM can then be successfully transmitted on a dish

Cell passaging is used to form smaller clusters of cells on a new culture surface [ 21 ]. There are four important passaging procedures.

Enzymatic dissociation is a cutting action of enzymes on proteins and adhesion domains that bind the colony. It is a gentler method than the manual passage. It is crucial to not leave hESCs alone after passaging. Solitary cells are more sensitive and can easily undergo cell death; collagenase type IV is an example [ 22 , 23 ].

Manual passage , on the other hand, focuses on using cell scratchers. The selection of certain cells is not necessary. This should be done in the early stages of cell line derivation [ 24 ].

Trypsin utilization allows a healthy, automated hESC passage. Good Manufacturing Practice (GMP)-grade recombinant trypsin is widely available in this procedure [ 24 ]. However, there is a risk of decreasing the pluripotency and viability of stem cells [ 25 ]. Trypsin utilization can be halted with an inhibitor of the protein rho-associated protein kinase (ROCK) [ 26 ].

Ethylenediaminetetraacetic acid ( EDTA ) indirectly suppresses cell-to-cell connections by chelating divalent cations. Their suppression promotes cell dissociation [ 27 ].

Stem cells require a mixture of growth factors and nutrients to differentiate and develop. The medium should be changed each day.

Traditional culture methods used for hESCs are mouse embryonic fibroblasts (MEFs) as a feeder layer and bovine serum [ 28 ] as a medium. Martin et al. [ 29 ] demonstrated that hESCs cultured in the presence of animal products express the non-human sialic acid, N -glycolylneuraminic acid (NeuGc). Feeder layers prevent uncontrolled proliferation with factors such as leukaemia inhibitory factor (LIF) [ 30 ].

First feeder layer-free culture can be supplemented with serum replacement, combined with laminin [ 31 ]. This causes stable karyotypes of stem cells and pluripotency lasting for over a year.

Initial culturing media can be serum (e.g. foetal calf serum FCS), artificial replacement such as synthetic serum substitute (SSS), knockout serum replacement (KOSR), or StemPro [ 32 ]. The simplest culture medium contains only eight essential elements: DMEM/F12 medium, selenium, NaHCO 3, l -ascorbic acid, transferrin, insulin, TGFβ1, and FGF2 [ 33 ]. It is not yet fully known whether culture systems developed for hESCs can be allowed without adaptation in iPSC cultures.

Turning point in stem cell therapy

The turning point in stem cell therapy appeared in 2006, when scientists Shinya Yamanaka, together with Kazutoshi Takahashi, discovered that it is possible to reprogram multipotent adult stem cells to the pluripotent state. This process avoided endangering the foetus’ life in the process. Retrovirus-mediated transduction of mouse fibroblasts with four transcription factors (Oct-3/4, Sox2, KLF4, and c-Myc) [ 34 ] that are mainly expressed in embryonic stem cells could induce the fibroblasts to become pluripotent (Fig. 5 ) [ 35 ]. This new form of stem cells was named iPSCs. One year later, the experiment also succeeded with human cells [ 36 ]. After this success, the method opened a new field in stem cell research with a generation of iPSC lines that can be customized and biocompatible with the patient. Recently, studies have focused on reducing carcinogenesis and improving the conduction system.

Retroviral-mediated transduction induces pluripotency in isolated patient somatic cells. Target cells lose their role as somatic cells and, once again, become pluripotent and can differentiate into any cell type of human body

The turning point was influenced by former discoveries that happened in 1962 and 1987.

The former discovery was about scientist John Gurdon successfully cloning frogs by transferring a nucleus from a frog’s somatic cells into an oocyte. This caused a complete reversion of somatic cell development [ 37 ]. The results of his experiment became an immense discovery since it was previously believed that cell differentiation is a one-way street only, but his experiment suggested the opposite and demonstrated that it is even possible for a somatic cell to again acquire pluripotency [ 38 ].

The latter was a discovery made by Davis R.L. that focused on fibroblast DNA subtraction. Three genes were found that originally appeared in myoblasts. The enforced expression of only one of the genes, named myogenic differentiation 1 (Myod1), caused the conversion of fibroblasts into myoblasts, showing that reprogramming cells is possible, and it can even be used to transform cells from one lineage to another [ 39 ].

Although pluripotency can occur naturally only in embryonic stem cells, it is possible to induce terminally differentiated cells to become pluripotent again. The process of direct reprogramming converts differentiated somatic cells into iPSC lines that can form all cell types of an organism. Reprogramming focuses on the expression of oncogenes such as Myc and Klf4 (Kruppel-like factor 4). This process is enhanced by a downregulation of genes promoting genome stability, such as p53. Additionally, cell reprogramming involves histone alteration. All these processes can cause potential mutagenic risk and later lead to an increased number of mutations. Quinlan et al. [ 40 ] checked fully pluripotent mouse iPSCs using whole genome DNA sequencing and structural variation (SV) detection algorithms. Based on those studies, it was confirmed that although there were single mutations in the non-genetic region, there were non-retrotransposon insertions. This led to the conclusion that current reprogramming methods can produce fully pluripotent iPSCs without severe genomic alterations.

During the course of development from pluripotent hESCs to differentiated somatic cells, crucial changes appear in the epigenetic structure of these cells. There is a restriction or permission of the transcription of genes relevant to each cell type. When somatic cells are being reprogrammed using transcription factors, all the epigenetic architecture has to be reconditioned to achieve iPSCs with pluripotency [ 41 ]. However, cells of each tissue undergo specific somatic genomic methylation. This influences transcription, which can further cause alterations in induced pluripotency [ 42 ].

Source of iPSCs

Because pluripotent cells can propagate indefinitely and differentiate into any kind of cell, they can be an unlimited source, either for replacing lost or diseased tissues. iPSCs bypass the need for embryos in stem cell therapy. Because they are made from the patient’s own cells, they are autologous and no longer generate any risk of immune rejection.

At first, fibroblasts were used as a source of iPSCs. Because a biopsy was needed to achieve these types of cells, the technique underwent further research. Researchers investigated whether more accessible cells could be used in the method. Further, other cells were used in the process: peripheral blood cells, keratinocytes, and renal epithelial cells found in urine. An alternative strategy to stem cell transplantation can be stimulating a patient’s endogenous stem cells to divide or differentiate, occurring naturally when skin wounds are healing. In 2008, pancreatic exocrine cells were shown to be reprogrammed to functional, insulin-producing beta cells [ 43 ].

The best stem cell source appears to be the fibroblasts, which is more tempting in the case of logistics since its stimulation can be fast and better controlled [ 44 ].

Teratoma formation assay

The self-renewal and differentiation capabilities of iPSCs have gained significant interest and attention in regenerative medicine sciences. To study their abilities, a quality-control assay is needed, of which one of the most important is the teratoma formation assay. Teratomas are benign tumours. Teratomas are capable of rapid growth in vivo and are characteristic because of their ability to develop into tissues of all three germ layers simultaneously. Because of the high pluripotency of teratomas, this formation assay is considered an assessment of iPSC’s abilities [ 45 ].

Teratoma formation rate, for instance, was observed to be elevated in human iPSCs compared to that in hESCs [ 46 ]. This difference may be connected to different differentiation methods and cell origins. Most commonly, the teratoma assay involves an injection of examined iPSCs subcutaneously or under the testis or kidney capsule in mice, which are immune-deficient [ 47 ]. After injection, an immature but recognizable tissue can be observed, such as the kidney tubules, bone, cartilage, or neuroepithelium [ 30 ]. The injection site may have an impact on the efficiency of teratoma formation [ 48 ].

There are three groups of markers used in this assay to differentiate the cells of germ layers. For endodermal tissue, there is insulin/C-peptide and alpha-1 antitrypsin [ 49 ]. For the mesoderm, derivatives can be used, e.g. cartilage matrix protein for the bone and alcian blue for the cartilage. As ectodermal markers, class III B botulin or keratin can be used for keratinocytes.

Teratoma formation assays are considered the gold standard for demonstrating the pluripotency of human iPSCs, demonstrating their possibilities under physiological conditions. Due to their actual tissue formation, they could be used for the characterization of many cell lineages [ 50 ].

Directed differentiation

To be useful in therapy, stem cells must be converted into desired cell types as necessary or else the whole regenerative medicine process will be pointless. Differentiation of ESCs is crucial because undifferentiated ESCs can cause teratoma formation in vivo. Understanding and using signalling pathways for differentiation is an important method in successful regenerative medicine. In directed differentiation, it is likely to mimic signals that are received by cells when they undergo successive stages of development [ 51 ]. The extracellular microenvironment plays a significant role in controlling cell behaviour. By manipulating the culture conditions, it is possible to restrict specific differentiation pathways and generate cultures that are enriched in certain precursors in vitro. However, achieving a similar effect in vivo is challenging. It is crucial to develop culture conditions that will allow the promotion of homogenous and enhanced differentiation of ESCs into functional and desired tissues.

Regarding the self-renewal of embryonic stem cells, Hwang et al. [ 52 ] noted that the ideal culture method for hESC-based cell and tissue therapy would be a defined culture free of either the feeder layer or animal components. This is because cell and tissue therapy requires the maintenance of large quantities of undifferentiated hESCs, which does not make feeder cells suitable for such tasks.

Most directed differentiation protocols are formed to mimic the development of an inner cell mass during gastrulation. During this process, pluripotent stem cells differentiate into ectodermal, mesodermal, or endodermal progenitors. Mall molecules or growth factors induce the conversion of stem cells into appropriate progenitor cells, which will later give rise to the desired cell type. There is a variety of signal intensities and molecular families that may affect the establishment of germ layers in vivo, such as fibroblast growth factors (FGFs) [ 53 ]; the Wnt family [ 54 ] or superfamily of transforming growth factors—β(TGFβ); and bone morphogenic proteins (BMP) [ 55 ]. Each candidate factor must be tested on various concentrations and additionally applied to various durations because the precise concentrations and times during which developing cells in embryos are influenced during differentiation are unknown. For instance, molecular antagonists of endogenous BMP and Wnt signalling can be used for ESC formation of ectoderm [ 56 ]. However, transient Wnt and lower concentrations of the TGFβ family trigger mesodermal differentiation [ 57 ]. Regarding endoderm formation, a higher activin A concentration may be required [ 58 , 59 ].

There are numerous protocols about the methods of forming progenitors of cells of each of germ layers, such as cardiomyocytes [ 60 ], hepatocytes [ 61 ], renal cells [ 62 ], lung cells [ 63 , 64 ], motor neurons [ 65 ], intestinal cells [ 66 ], or chondrocytes [ 67 ].

Directed differentiation of either iPSCs or ESCs into, e.g. hepatocytes, could influence and develop the study of the molecular mechanisms in human liver development. In addition, it could also provide the possibility to form exogenous hepatocytes for drug toxicity testing [ 68 ].

Levels of concentration and duration of action with a specific signalling molecule can cause a variety of factors. Unfortunately, for now, a high cost of recombinant factors is likely to limit their use on a larger scale in medicine. The more promising technique focuses on the use of small molecules. These can be used for either activating or deactivating specific signalling pathways. They enhance reprogramming efficiency by creating cells that are compatible with the desired type of tissue. It is a cheaper and non-immunogenic method.

One of the successful examples of small-molecule cell therapies is antagonists and agonists of the Hedgehog pathway. They show to be very useful in motor neuron regeneration [ 69 ]. Endogenous small molecules with their function in embryonic development can also be used in in vitro methods to induce the differentiation of cells; for example, retinoic acid, which is responsible for patterning the nervous system in vivo [ 70 ], surprisingly induced retinal cell formation when the laboratory procedure involved hESCs [ 71 ].

The efficacy of differentiation factors depends on functional maturity, efficiency, and, finally, introducing produced cells to their in vivo equivalent. Topography, shear stress, and substrate rigidity are factors influencing the phenotype of future cells [ 72 ].

The control of biophysical and biochemical signals, the biophysical environment, and a proper guide of hESC differentiation are important factors in appropriately cultured stem cells.

Stem cell utilization and their manufacturing standards and culture systems

The European Medicines Agency and the Food and Drug Administration have set Good Manufacturing Practice (GMP) guidelines for safe and appropriate stem cell transplantation. In the past, protocols used for stem cell transplantation required animal-derived products [ 73 ].

The risk of introducing animal antigens or pathogens caused a restriction in their use. Due to such limitations, the technique required an obvious update [ 74 ]. Now, it is essential to use xeno-free equivalents when establishing cell lines that are derived from fresh embryos and cultured from human feeder cell lines [ 75 ]. In this method, it is crucial to replace any non-human materials with xeno-free equivalents [ 76 ].

NutriStem with LN-511, TeSR2 with human recombinant laminin (LN-511), and RegES with human foreskin fibroblasts (HFFs) are commonly used xeno-free culture systems [ 33 ]. There are many organizations and international initiatives, such as the National Stem Cell Bank, that provide stem cell lines for treatment or medical research [ 77 ].

Stem cell use in medicine

Stem cells have great potential to become one of the most important aspects of medicine. In addition to the fact that they play a large role in developing restorative medicine, their study reveals much information about the complex events that happen during human development.

The difference between a stem cell and a differentiated cell is reflected in the cells’ DNA. In the former cell, DNA is arranged loosely with working genes. When signals enter the cell and the differentiation process begins, genes that are no longer needed are shut down, but genes required for the specialized function will remain active. This process can be reversed, and it is known that such pluripotency can be achieved by interaction in gene sequences. Takahashi and Yamanaka [ 78 ] and Loh et al. [ 79 ] discovered that octamer-binding transcription factor 3 and 4 (Oct3/4), sex determining region Y (SRY)-box 2 and Nanog genes function as core transcription factors in maintaining pluripotency. Among them, Oct3/4 and Sox2 are essential for the generation of iPSCs.

Many serious medical conditions, such as birth defects or cancer, are caused by improper differentiation or cell division. Currently, several stem cell therapies are possible, among which are treatments for spinal cord injury, heart failure [ 80 ], retinal and macular degeneration [ 81 ], tendon ruptures, and diabetes type 1 [ 82 ]. Stem cell research can further help in better understanding stem cell physiology. This may result in finding new ways of treating currently incurable diseases.

Haematopoietic stem cell transplantation

Haematopoietic stem cells are important because they are by far the most thoroughly characterized tissue-specific stem cell; after all, they have been experimentally studied for more than 50 years. These stem cells appear to provide an accurate paradigm model system to study tissue-specific stem cells, and they have potential in regenerative medicine.

Multipotent haematopoietic stem cell (HSC) transplantation is currently the most popular stem cell therapy. Target cells are usually derived from the bone marrow, peripheral blood, or umbilical cord blood [ 83 ]. The procedure can be autologous (when the patient’s own cells are used), allogenic (when the stem cell comes from a donor), or syngeneic (from an identical twin). HSCs are responsible for the generation of all functional haematopoietic lineages in blood, including erythrocytes, leukocytes, and platelets. HSC transplantation solves problems that are caused by inappropriate functioning of the haematopoietic system, which includes diseases such as leukaemia and anaemia. However, when conventional sources of HSC are taken into consideration, there are some important limitations. First, there is a limited number of transplantable cells, and an efficient way of gathering them has not yet been found. There is also a problem with finding a fitting antigen-matched donor for transplantation, and viral contamination or any immunoreactions also cause a reduction in efficiency in conventional HSC transplantations. Haematopoietic transplantation should be reserved for patients with life-threatening diseases because it has a multifactorial character and can be a dangerous procedure. iPSC use is crucial in this procedure. The use of a patient’s own unspecialized somatic cells as stem cells provides the greatest immunological compatibility and significantly increases the success of the procedure.

Stem cells as a target for pharmacological testing

Stem cells can be used in new drug tests. Each experiment on living tissue can be performed safely on specific differentiated cells from pluripotent cells. If any undesirable effect appears, drug formulas can be changed until they reach a sufficient level of effectiveness. The drug can enter the pharmacological market without harming any live testers. However, to test the drugs properly, the conditions must be equal when comparing the effects of two drugs. To achieve this goal, researchers need to gain full control of the differentiation process to generate pure populations of differentiated cells.

Stem cells as an alternative for arthroplasty

One of the biggest fears of professional sportsmen is getting an injury, which most often signifies the end of their professional career. This applies especially to tendon injuries, which, due to current treatment options focusing either on conservative or surgical treatment, often do not provide acceptable outcomes. Problems with the tendons start with their regeneration capabilities. Instead of functionally regenerating after an injury, tendons merely heal by forming scar tissues that lack the functionality of healthy tissues. Factors that may cause this failed healing response include hypervascularization, deposition of calcific materials, pain, or swelling [ 84 ].

Additionally, in addition to problems with tendons, there is a high probability of acquiring a pathological condition of joints called osteoarthritis (OA) [ 85 ]. OA is common due to the avascular nature of articular cartilage and its low regenerative capabilities [ 86 ]. Although arthroplasty is currently a common procedure in treating OA, it is not ideal for younger patients because they can outlive the implant and will require several surgical procedures in the future. These are situations where stem cell therapy can help by stopping the onset of OA [ 87 ]. However, these procedures are not well developed, and the long-term maintenance of hyaline cartilage requires further research.

Osteonecrosis of the femoral hip (ONFH) is a refractory disease associated with the collapse of the femoral head and risk of hip arthroplasty in younger populations [ 88 ]. Although total hip arthroplasty (THA) is clinically successful, it is not ideal for young patients, mostly due to the limited lifetime of the prosthesis. An increasing number of clinical studies have evaluated the therapeutic effect of stem cells on ONFH. Most of the authors demonstrated positive outcomes, with reduced pain, improved function, or avoidance of THA [ 89 , 90 , 91 ].

Rejuvenation by cell programming

Ageing is a reversible epigenetic process. The first cell rejuvenation study was published in 2011 [ 92 ]. Cells from aged individuals have different transcriptional signatures, high levels of oxidative stress, dysfunctional mitochondria, and shorter telomeres than in young cells [ 93 ]. There is a hypothesis that when human or mouse adult somatic cells are reprogrammed to iPSCs, their epigenetic age is virtually reset to zero [ 94 ]. This was based on an epigenetic model, which explains that at the time of fertilization, all marks of parenteral ageing are erased from the zygote’s genome and its ageing clock is reset to zero [ 95 ].

In their study, Ocampo et al. [ 96 ] used Oct4, Sox2, Klf4, and C-myc genes (OSKM genes) and affected pancreas and skeletal muscle cells, which have poor regenerative capacity. Their procedure revealed that these genes can also be used for effective regenerative treatment [ 97 ]. The main challenge of their method was the need to employ an approach that does not use transgenic animals and does not require an indefinitely long application. The first clinical approach would be preventive, focused on stopping or slowing the ageing rate. Later, progressive rejuvenation of old individuals can be attempted. In the future, this method may raise some ethical issues, such as overpopulation, leading to lower availability of food and energy.

For now, it is important to learn how to implement cell reprogramming technology in non-transgenic elder animals and humans to erase marks of ageing without removing the epigenetic marks of cell identity.

Cell-based therapies

Stem cells can be induced to become a specific cell type that is required to repair damaged or destroyed tissues (Fig. 6 ). Currently, when the need for transplantable tissues and organs outweighs the possible supply, stem cells appear to be a perfect solution for the problem. The most common conditions that benefit from such therapy are macular degenerations [ 98 ], strokes [ 99 ], osteoarthritis [ 89 , 90 ], neurodegenerative diseases, and diabetes [ 100 ]. Due to this technique, it can become possible to generate healthy heart muscle cells and later transplant them to patients with heart disease.

Stem cell experiments on animals. These experiments are one of the many procedures that proved stem cells to be a crucial factor in future regenerative medicine

In the case of type 1 diabetes, insulin-producing cells in the pancreas are destroyed due to an autoimmunological reaction. As an alternative to transplantation therapy, it can be possible to induce stem cells to differentiate into insulin-producing cells [ 101 ].

Stem cells and tissue banks

iPS cells with their theoretically unlimited propagation and differentiation abilities are attractive for the present and future sciences. They can be stored in a tissue bank to be an essential source of human tissue used for medical examination. The problem with conventional differentiated tissue cells held in the laboratory is that their propagation features diminish after time. This does not occur in iPSCs.

The umbilical cord is known to be rich in mesenchymal stem cells. Due to its cryopreservation immediately after birth, its stem cells can be successfully stored and used in therapies to prevent the future life-threatening diseases of a given patient.

Stem cells of human exfoliated deciduous teeth (SHED) found in exfoliated deciduous teeth has the ability to develop into more types of body tissues than other stem cells [ 102 ] (Table 1 ). Techniques of their collection, isolation, and storage are simple and non-invasive. Among the advantages of banking, SHED cells are:

Guaranteed donor-match autologous transplant that causes no immune reaction and rejection of cells [ 103 ]

Simple and painless for both child and parent

Less than one third of the cost of cord blood storage

Not subject to the same ethical concerns as embryonic stem cells [ 104 ]

In contrast to cord blood stem cells, SHED cells are able to regenerate into solid tissues such as connective, neural, dental, or bone tissue [ 105 , 106 ]

SHED can be useful for close relatives of the donor

Fertility diseases

In 2011, two researchers, Katsuhiko Hayashi et al. [ 107 ], showed in an experiment on mice that it is possible to form sperm from iPSCs. They succeeded in delivering healthy and fertile pups in infertile mice. The experiment was also successful for female mice, where iPSCs formed fully functional eggs .

Young adults at risk of losing their spermatogonial stem cells (SSC), mostly cancer patients, are the main target group that can benefit from testicular tissue cryopreservation and autotransplantation. Effective freezing methods for adult and pre-pubertal testicular tissue are available [ 108 ].

Qiuwan et al. [ 109 ] provided important evidence that human amniotic epithelial cell (hAEC) transplantation could effectively improve ovarian function by inhibiting cell apoptosis and reducing inflammation in injured ovarian tissue of mice, and it could be a promising strategy for the management of premature ovarian failure or insufficiency in female cancer survivors.

For now, reaching successful infertility treatments in humans appears to be only a matter of time, but there are several challenges to overcome. First, the process needs to have high efficiency; second, the chances of forming tumours instead of eggs or sperm must be maximally reduced. The last barrier is how to mature human sperm and eggs in the lab without transplanting them to in vivo conditions, which could cause either a tumour risk or an invasive procedure.

Therapy for incurable neurodegenerative diseases

Thanks to stem cell therapy, it is possible not only to delay the progression of incurable neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease (AD), and Huntington disease, but also, most importantly, to remove the source of the problem. In neuroscience, the discovery of neural stem cells (NSCs) has nullified the previous idea that adult CNS were not capable of neurogenesis [ 110 , 111 ]. Neural stem cells are capable of improving cognitive function in preclinical rodent models of AD [ 112 , 113 , 114 ]. Awe et al. [ 115 ] clinically derived relevant human iPSCs from skin punch biopsies to develop a neural stem cell-based approach for treating AD. Neuronal degeneration in Parkinson’s disease (PD) is focal, and dopaminergic neurons can be efficiently generated from hESCs. PD is an ideal disease for iPSC-based cell therapy [ 116 ]. However, this therapy is still in an experimental phase ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539501 /). Brain tissue from aborted foetuses was used on patients with Parkinson’s disease [ 117 ]. Although the results were not uniform, they showed that therapies with pure stem cells are an important and achievable therapy.

Stem cell use in dentistry

Teeth represent a very challenging material for regenerative medicine. They are difficult to recreate because of their function in aspects such as articulation, mastication, or aesthetics due to their complicated structure. Currently, there is a chance for stem cells to become more widely used than synthetic materials. Teeth have a large advantage of being the most natural and non-invasive source of stem cells.

For now, without the use of stem cells, the most common periodontological treatments are either growth factors, grafts, or surgery. For example, there are stem cells in periodontal ligament [ 118 , 119 ], which are capable of differentiating into osteoblasts or cementoblasts, and their functions were also assessed in neural cells [ 120 ]. Tissue engineering is a successful method for treating periodontal diseases. Stem cells of the root apical areas are able to recreate periodontal ligament. One of the possible methods of tissue engineering in periodontology is gene therapy performed using adenoviruses-containing growth factors [ 121 ].

As a result of animal studies, dentin regeneration is an effective process that results in the formation of dentin bridges [ 122 ].

Enamel is more difficult to regenerate than dentin. After the differentiation of ameloblastoma cells into the enamel, the former is destroyed, and reparation is impossible. Medical studies have succeeded in differentiating bone marrow stem cells into ameloblastoma [ 123 ].

Healthy dental tissue has a high amount of regular stem cells, although this number is reduced when tissue is either traumatized or inflamed [ 124 ]. There are several dental stem cell groups that can be isolated (Fig. 7 ).

Localization of stem cells in dental tissues. Dental pulp stem cells (DPSCs) and human deciduous teeth stem cells (SHED) are located in the dental pulp. Periodontal ligaments stem cells are located in the periodontal ligament. Apical papilla consists of stem cells from the apical papilla (SCAP)

Dental pulp stem cell (DPSC)

These were the first dental stem cells isolated from the human dental pulp, which were [ 125 ] located inside dental pulp (Table 2 ). They have osteogenic and chondrogenic potential. Mesenchymal stem cells (MSCs) of the dental pulp, when isolated, appear highly clonogenic; they can be isolated from adult tissue (e.g. bone marrow, adipose tissue) and foetal (e.g. umbilical cord) [ 126 ] tissue, and they are able to differentiate densely [ 127 ]. MSCs differentiate into odontoblast-like cells and osteoblasts to form dentin and bone. Their best source locations are the third molars [ 125 ]. DPSCs are the most useful dental source of tissue engineering due to their easy surgical accessibility, cryopreservation possibility, increased production of dentin tissues compared to non-dental stem cells, and their anti-inflammatory abilities. These cells have the potential to be a source for maxillofacial and orthopaedic reconstructions or reconstructions even beyond the oral cavity. DPSCs are able to generate all structures of the developed tooth [ 128 ]. In particular, beneficial results in the use of DPSCs may be achieved when combined with other new therapies, such as periodontal tissue photobiomodulation (laser stimulation), which is an efficient technique in the stimulation of proliferation and differentiation into distinct cell types [ 129 ]. DPSCs can be induced to form neural cells to help treat neurological deficits.

Stem cells of human exfoliated deciduous teeth (SHED) have a faster rate of proliferation than DPSCs and differentiate into an even greater number of cells, e.g. other mesenchymal and non-mesenchymal stem cell derivatives, such as neural cells [ 130 ]. These cells possess one major disadvantage: they form a non-complete dentin/pulp-like complex in vivo. SHED do not undergo the same ethical concerns as embryonic stem cells. Both DPSCs and SHED are able to form bone-like tissues in vivo [ 131 ] and can be used for periodontal, dentin, or pulp regeneration. DPSCs and SHED can be used in treating, for example, neural deficits [ 132 ]. DPSCs alone were tested and successfully applied for alveolar bone and mandible reconstruction [ 133 ].

Periodontal ligament stem cells (PDLSCs)

These cells are used in periodontal ligament or cementum tissue regeneration. They can differentiate into mesenchymal cell lineages to produce collagen-forming cells, adipocytes, cementum tissue, Sharpey’s fibres, and osteoblast-like cells in vitro. PDLSCs exist both on the root and alveolar bone surfaces; however, on the latter, these cells have better differentiation abilities than on the former [ 134 ]. PDLSCs have become the first treatment for periodontal regeneration therapy because of their safety and efficiency [ 135 , 136 ].

Stem cells from apical papilla (SCAP)

These cells are mesenchymal structures located within immature roots. They are isolated from human immature permanent apical papilla. SCAP are the source of odontoblasts and cause apexogenesis. These stem cells can be induced in vitro to form odontoblast-like cells, neuron-like cells, or adipocytes. SCAP have a higher capacity of proliferation than DPSCs, which makes them a better choice for tissue regeneration [ 137 , 138 ].

Dental follicle stem cells (DFCs)

These cells are loose connective tissues surrounding the developing tooth germ. DFCs contain cells that can differentiate into cementoblasts, osteoblasts, and periodontal ligament cells [ 139 , 140 ]. Additionally, these cells proliferate after even more than 30 passages [ 141 ]. DFCs are most commonly extracted from the sac of a third molar. When DFCs are combined with a treated dentin matrix, they can form a root-like tissue with a pulp-dentin complex and eventually form tooth roots [ 141 ]. When DFC sheets are induced by Hertwig’s epithelial root sheath cells, they can produce periodontal tissue; thus, DFCs represent a very promising material for tooth regeneration [ 142 ].

Pulp regeneration in endodontics

Dental pulp stem cells can differentiate into odontoblasts. There are few methods that enable the regeneration of the pulp.

The first is an ex vivo method. Proper stem cells are grown on a scaffold before they are implanted into the root channel [ 143 ].

The second is an in vivo method. This method focuses on injecting stem cells into disinfected root channels after the opening of the in vivo apex. Additionally, the use of a scaffold is necessary to prevent the movement of cells towards other tissues. For now, only pulp-like structures have been created successfully.

Methods of placing stem cells into the root channel constitute are either soft scaffolding [ 144 ] or the application of stem cells in apexogenesis or apexification. Immature teeth are the best source [ 145 ]. Nerve and blood vessel network regeneration are extremely vital to keep pulp tissue healthy.

The potential of dental stem cells is mainly regarding the regeneration of damaged dentin and pulp or the repair of any perforations; in the future, it appears to be even possible to generate the whole tooth. Such an immense success would lead to the gradual replacement of implant treatments. Mandibulary and maxillary defects can be one of the most complicated dental problems for stem cells to address.

Acquiring non-dental tissue cells by dental stem cell differentiation

In 2013, it was reported that it is possible to grow teeth from stem cells obtained extra-orally, e.g. from urine [ 146 ]. Pluripotent stem cells derived from human urine were induced and generated tooth-like structures. The physical properties of the structures were similar to natural ones except for hardness [ 127 ]. Nonetheless, it appears to be a very promising technique because it is non-invasive and relatively low-cost, and somatic cells can be used instead of embryonic cells. More importantly, stem cells derived from urine did not form any tumours, and the use of autologous cells reduces the chances of rejection [ 147 ].

Use of graphene in stem cell therapy

Over recent years, graphene and its derivatives have been increasingly used as scaffold materials to mediate stem cell growth and differentiation [ 148 ]. Both graphene and graphene oxide (GO) represent high in-plane stiffness [ 149 ]. Because graphene has carbon and aromatic network, it works either covalently or non-covalently with biomolecules; in addition to its superior mechanical properties, graphene offers versatile chemistry. Graphene exhibits biocompatibility with cells and their proper adhesion. It also tested positively for enhancing the proliferation or differentiation of stem cells [ 148 ]. After positive experiments, graphene revealed great potential as a scaffold and guide for specific lineages of stem cell differentiation [ 150 ]. Graphene has been successfully used in the transplantation of hMSCs and their guided differentiation to specific cells. The acceleration skills of graphene differentiation and division were also investigated. It was discovered that graphene can serve as a platform with increased adhesion for both growth factors and differentiation chemicals. It was also discovered that π-π binding was responsible for increased adhesion and played a crucial role in inducing hMSC differentiation [ 150 ].

Therapeutic potential of extracellular vesicle-based therapies

Extracellular vesicles (EVs) can be released by virtually every cell of an organism, including stem cells [ 151 ], and are involved in intercellular communication through the delivery of their mRNAs, lipids, and proteins. As Oh et al. [ 152 ] prove, stem cells, together with their paracrine factors—exosomes—can become potential therapeutics in the treatment of, e.g. skin ageing. Exosomes are small membrane vesicles secreted by most cells (30–120 nm in diameter) [ 153 ]. When endosomes fuse with the plasma membrane, they become exosomes that have messenger RNAs (mRNAs) and microRNAs (miRNAs), some classes of non-coding RNAs (IncRNAs) and several proteins that originate from the host cell [ 154 ]. IncRNAs can bind to specific loci and create epigenetic regulators, which leads to the formation of epigenetic modifications in recipient cells. Because of this feature, exosomes are believed to be implicated in cell-to-cell communication and the progression of diseases such as cancer [ 155 ]. Recently, many studies have also shown the therapeutic use of exosomes derived from stem cells, e.g. skin damage and renal or lung injuries [ 156 ].

In skin ageing, the most important factor is exposure to UV light, called “photoageing” [ 157 ], which causes extrinsic skin damage, characterized by dryness, roughness, irregular pigmentation, lesions, and skin cancers. In intrinsic skin ageing, on the other hand, the loss of elasticity is a characteristic feature. The skin dermis consists of fibroblasts, which are responsible for the synthesis of crucial skin elements, such as procollagen or elastic fibres. These elements form either basic framework extracellular matrix constituents of the skin dermis or play a major role in tissue elasticity. Fibroblast efficiency and abundance decrease with ageing [ 158 ]. Stem cells can promote the proliferation of dermal fibroblasts by secreting cytokines such as platelet-derived growth factor (PDGF), transforming growth factor β (TGF-β), and basic fibroblast growth factor. Huh et al. [ 159 ] mentioned that a medium of human amniotic fluid-derived stem cells (hAFSC) positively affected skin regeneration after longwave UV-induced (UVA, 315–400 nm) photoageing by increasing the proliferation and migration of dermal fibroblasts. It was discovered that, in addition to the induction of fibroblast physiology, hAFSC transplantation also improved diseases in cases of renal pathology, various cancers, or stroke [ 160 , 161 ].

Oh [ 162 ] also presented another option for the treatment of skin wounds, either caused by physical damage or due to diabetic ulcers. Induced pluripotent stem cell-conditioned medium (iPSC-CM) without any animal-derived components induced dermal fibroblast proliferation and migration.

Natural cutaneous wound healing is divided into three steps: haemostasis/inflammation, proliferation, and remodelling. During the crucial step of proliferation, fibroblasts migrate and increase in number, indicating that it is a critical step in skin repair, and factors such as iPSC-CM that impact it can improve the whole cutaneous wound healing process. Paracrine actions performed by iPSCs are also important for this therapeutic effect [ 163 ]. These actions result in the secretion of cytokines such as TGF-β, interleukin (IL)-6, IL-8, monocyte chemotactic protein-1 (MCP-1), vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA (PDGF-AA), and basic fibroblast growth factor (bFGF). Bae et al. [ 164 ] mentioned that TGF-β induced the migration of keratinocytes. It was also demonstrated that iPSC factors can enhance skin wound healing in vivo and in vitro when Zhou et al. [ 165 ] enhanced wound healing, even after carbon dioxide laser resurfacing in an in vivo study.

Peng et al. [ 166 ] investigated the effects of EVs derived from hESCs on in vitro cultured retinal glial, progenitor Müller cells, which are known to differentiate into retinal neurons. EVs appear heterogeneous in size and can be internalized by cultured Müller cells, and their proteins are involved in the induction and maintenance of stem cell pluripotency. These stem cell-derived vesicles were responsible for the neuronal trans-differentiation of cultured Müller cells exposed to them. However, the research article points out that the procedure was accomplished only on in vitro acquired retina.

Challenges concerning stem cell therapy

Although stem cells appear to be an ideal solution for medicine, there are still many obstacles that need to be overcome in the future. One of the first problems is ethical concern.

The most common pluripotent stem cells are ESCs. Therapies concerning their use at the beginning were, and still are, the source of ethical conflicts. The reason behind it started when, in 1998, scientists discovered the possibility of removing ESCs from human embryos. Stem cell therapy appeared to be very effective in treating many, even previously incurable, diseases. The problem was that when scientists isolated ESCs in the lab, the embryo, which had potential for becoming a human, was destroyed (Fig. 8 ). Because of this, scientists, seeing a large potential in this treatment method, focused their efforts on making it possible to isolate stem cells without endangering their source—the embryo.

Use of inner cell mass pluripotent stem cells and their stimulation to differentiate into desired cell types

For now, while hESCs still remain an ethically debatable source of cells, they are potentially powerful tools to be used for therapeutic applications of tissue regeneration. Because of the complexity of stem cell control systems, there is still much to be learned through observations in vitro. For stem cells to become a popular and widely accessible procedure, tumour risk must be assessed. The second problem is to achieve successful immunological tolerance between stem cells and the patient’s body. For now, one of the best ideas is to use the patient’s own cells and devolve them into their pluripotent stage of development.

New cells need to have the ability to fully replace lost or malfunctioning natural cells. Additionally, there is a concern about the possibility of obtaining stem cells without the risk of morbidity or pain for either the patient or the donor. Uncontrolled proliferation and differentiation of cells after implementation must also be assessed before its use in a wide variety of regenerative procedures on living patients [ 167 ].

One of the arguments that limit the use of iPSCs is their infamous role in tumourigenicity. There is a risk that the expression of oncogenes may increase when cells are being reprogrammed. In 2008, a technique was discovered that allowed scientists to remove oncogenes after a cell achieved pluripotency, although it is not efficient yet and takes a longer amount of time. The process of reprogramming may be enhanced by deletion of the tumour suppressor gene p53, but this gene also acts as a key regulator of cancer, which makes it impossible to remove in order to avoid more mutations in the reprogrammed cell. The low efficiency of the process is another problem, which is progressively becoming reduced with each year. At first, the rate of somatic cell reprogramming in Yamanaka’s study was up to 0.1%. The use of transcription factors creates a risk of genomic insertion and further mutation of the target cell genome. For now, the only ethically acceptable operation is an injection of hESCs into mouse embryos in the case of pluripotency evaluation [ 168 ].

Stem cell obstacles in the future

Pioneering scientific and medical advances always have to be carefully policed in order to make sure they are both ethical and safe. Because stem cell therapy already has a large impact on many aspects of life, it should not be treated differently.

Currently, there are several challenges concerning stem cells. First, the most important one is about fully understanding the mechanism by which stem cells function first in animal models. This step cannot be avoided. For the widespread, global acceptance of the procedure, fear of the unknown is the greatest challenge to overcome.

The efficiency of stem cell-directed differentiation must be improved to make stem cells more reliable and trustworthy for a regular patient. The scale of the procedure is another challenge. Future stem cell therapies may be a significant obstacle. Transplanting new, fully functional organs made by stem cell therapy would require the creation of millions of working and biologically accurate cooperating cells. Bringing such complicated procedures into general, widespread regenerative medicine will require interdisciplinary and international collaboration.

The identification and proper isolation of stem cells from a patient’s tissues is another challenge. Immunological rejection is a major barrier to successful stem cell transplantation. With certain types of stem cells and procedures, the immune system may recognize transplanted cells as foreign bodies, triggering an immune reaction resulting in transplant or cell rejection.

One of the ideas that can make stem cells a “failsafe” is about implementing a self-destruct option if they become dangerous. Further development and versatility of stem cells may cause reduction of treatment costs for people suffering from currently incurable diseases. When facing certain organ failure, instead of undergoing extraordinarily expensive drug treatment, the patient would be able to utilize stem cell therapy. The effect of a successful operation would be immediate, and the patient would avoid chronic pharmacological treatment and its inevitable side effects.

Although these challenges facing stem cell science can be overwhelming, the field is making great advances each day. Stem cell therapy is already available for treating several diseases and conditions. Their impact on future medicine appears to be significant.

After several decades of experiments, stem cell therapy is becoming a magnificent game changer for medicine. With each experiment, the capabilities of stem cells are growing, although there are still many obstacles to overcome. Regardless, the influence of stem cells in regenerative medicine and transplantology is immense. Currently, untreatable neurodegenerative diseases have the possibility of becoming treatable with stem cell therapy. Induced pluripotency enables the use of a patient’s own cells. Tissue banks are becoming increasingly popular, as they gather cells that are the source of regenerative medicine in a struggle against present and future diseases. With stem cell therapy and all its regenerative benefits, we are better able to prolong human life than at any time in history.

Abbreviations

Basic fibroblast growth factor

Bone morphogenic proteins

Dental follicle stem cells

Dental pulp stem cells

Embryonic bodies

Embryonic stem cells

Fibroblast growth factors

Good Manufacturing Practice

Graphene oxide

Human amniotic fluid-derived stem cells

Human embryonic stem cells

Human foreskin fibroblasts

Inner cell mass

Non-coding RNA

Induced pluripotent stem cells

In vitro fertilization

Knockout serum replacement

Leukaemia inhibitory factor

Monocyte chemotactic protein-1

Fibroblasts

Messenger RNA

Mesenchymal stem cells of dental pulp

Myogenic differentiation

Osteoarthritis

Octamer-binding transcription factor 3 and 4

Platelet-derived growth factor

Platelet-derived growth factor-AA

Periodontal ligament stem cells

Rho-associated protein kinase

Stem cells from apical papilla

Stem cells of human exfoliated deciduous teeth

Synthetic Serum Substitute

Trophectoderm

Vascular endothelial growth factor

Transforming growth factors

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Zakrzewski, W., Dobrzyński, M., Szymonowicz, M. et al. Stem cells: past, present, and future. Stem Cell Res Ther 10 , 68 (2019). https://doi.org/10.1186/s13287-019-1165-5

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Chapter 1, “Introduction to Stem Cells,” provides a comprehensive introductory overview of stem cells and gives a unique historical perspective with respect to advances in stem cell-related research throughout the millennia. The chapter begins with a brief history of stem cell research and expands upon historical implications in each section, outlining and describing seminal findings which have led to significant advancements in stem cell-based therapeutics and even diagnostics efforts. The chapter emphasizes the developmental and biological origins of stem cells, noting key molecular, morphological, and biochemical events occurring during embryonic development which set the stage for potency acquisition, transition and, ultimately, stem cell commitment to mature, differentiated lineages. All major stem cell types are introduced to the reader in both historical and developmental context. In addition, cutting-edge technologies such as induced pluripotency and nuclear transfer are described. The chapter concludes with an overview of the emerging stem cell industry emphasizing stem cells as the major regenerative medicine technological platform.

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Acknowledgments

The author would like to thank Dr. Valerie Jones and Dr. Taby Ahsan for critical review, comments, and suggestions regarding this material. The author would also like to acknowledge and thank all the authors, journals, and publishers who provided reprint permissions for the various figures and tables included herein. A special thanks is owed to Wikimedia Commons and its operators and generous donors for making numerous figures included in this chapter freely available for reprint without restrictions.

Rob Burgess, Ph.D. is Cofounder and Chairman of the Board of Medical Nanotechnologies, Inc. in Dallas, Texas, an Adjunct Professor in the Department of Molecular and Cell Biology at the University of Texas—Dallas and Director of Business Development for RayBiotech, Inc. in Norcross, Georgia. He can be reached at [email protected].

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Burgess, R. (2013). Introduction to Stem Cells. In: Sell, S. (eds) Stem Cells Handbook. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-7696-2_1

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Introduction to Stem Cell Therapy

Jesse k. biehl.

1 Department of Bioengineering, University of Illinois at Chicago

Brenda Russell

2 Department of Physiology and Biophysics and Department of Bioengineering, University of Illinois at Chicago

Stem cells have the ability to differentiate into specific cell types. The two defining characteristics of a stem cell are perpetual self-renewal and the ability to differentiate into a specialized adult cell type. There are two major classes of stem cells: pluripotent that can become any cell in the adult body, and multipotent that are restricted to becoming a more limited population of cells. Cell sources, characteristics, differentiation and therapeutic applications are discussed. Stem cells have great potential in tissue regeneration and repair but much still needs to be learned about their biology, manipulation and safety before their full therapeutic potential can be achieved.

Introduction

Stem cells have the ability to build every tissue in the human body, hence have great potential for future therapeutic uses in tissue regeneration and repair. In order for cells to fall under the definition of “stem cells,” they must display two essential characteristics. First, stem cells must have the ability of unlimited self-renewal to produce progeny exactly the same as the originating cell. This trait is also true of cancer cells that divide in an uncontrolled manner whereas stem cell division is highly regulated. Therefore, it is important to note the additional requirement for stem cells; they must be able to give rise to a specialized cell type that becomes part of the healthy animal. 1

The general designation, “stem cell” encompasses many distinct cell types. Commonly, the modifiers, “embryonic,” and “adult” are used to distinguish stem cells by the developmental stage of the animal from which they come, but these terms are becoming insufficient as new research has discovered how to turn fully differentiated adult cells back into embryonic stem cells and, conversely, adult stem cells, more correctly termed “somatic” stem cells meaning “from the body”, are found in the fetus, placenta, umbilical cord blood and infants. 2 Therefore, this review will sort stem cells into two categories based on their biologic properties - pluripotent stem cells and multipotent stem cells. Their sources, characteristics, differentiation and therapeutic applications are discussed.

Pluripotent stem cells are so named because they have the ability to differentiate into all cell types in the body. In natural development, pluripotent stem cells are only present for a very short period of time in the embryo before differentiating into the more specialized multipotent stem cells that eventually give rise to the specialized tissues of the body ( Figure 1 ). These more limited multipotent stem cells come in several subtypes: some can become only cells of a particular germ line (endoderm, mesoderm, ectoderm) and others, only cells of a particular tissue. In other words, pluripotent cells can eventually become any cell of the body by differentiating into multipotent stem cells that themselves go through a series of divisions into even more restricted specialized cells.

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During natural embryo development, cells undergo proliferation and specialization from the fertilized egg, to the blastocyst, to the gastrula during natural embryo development (left side of panel). Pluripotent, embryonic stem cells are derived from the inner cell mass of the blastoctyst (lightly shaded). Multipotent stem cells (diamond pattern, diagonal lines, and darker shade) are found in the developing gastrula or derived from pluripotent stem cells and are restricted to give rise to only cells of their respective germ layer.

Stem Cell Fates

Based on the two defining characteristics of stem cells (unlimited self-renewal and ability to differentiate), they can be described as having four outcomes or fates 3 ( Figure 2 ). A common fate for multipotent stem cells is to remain quiescent without dividing or differentiating, thus maintaining its place in the stem cell pool. An example of this is stem cells in the bone marrow that await activating signals from the body. A second fate of stem cells is symmetric self-renewal in which two daughter stem cells, exactly like the parent cell, arise from cell division. This does not result in differentiated progeny but does increase the pool of stem cells from which specialized cells can develop in subsequent divisions. The third fate, asymmetric self-renewal, occurs when a stem cell divides into two daughter cells, one a copy of the parent, the other a more specialized cell, named a somatic or progenitor cell. Asymmetric self-renewal results in the generation of differentiated progeny needed for natural tissue development/regeneration while also maintaining the stem cell pool for the future. The fourth fate is that in which a stem cell divides to produce two daughters both different from the parent cell. This results in greater proliferation of differentiated progeny with a net loss in the stem cell pool.

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Four potential outcomes of stem cells. A) Quiescence in which a stem cell does not divide but maintains the stem cell pool. B) Symmetric self-renewal where a stem cell divides into two daughter stem cells increasing the stem cell pool. C) Asymmetric self-renewal in which a stem cell divides into one differentiated daughter cell and one stem cell, maintaining the stem cell pool. D) Symmetric division without self-renewal where there is a loss in the stem cell pool but results in two differentiated daughter cells. (SC- Stem cell, DP-Differentiated progeny)

The factors that determine the fate of stem cells is the focus of intense research. Knowledge of the details could be clinically useful. For example, clinicians and scientists might direct a stem cell population to expand several fold through symmetrical self-renewal before differentiation into multipotent or more specialized progenitor cells. This would ensure a large, homogeneous population of cells at a useful differentiation stage that could be delivered to patients for successful tissue regeneration.

Sources of Stem Cells

Pluripotent.

Pluripotent stem cells being used in research today mainly come from embryos, hence the name, “embryonic stem cells”. Pre-implantation embryos a few days old contain only 10-15% pluripotent cells in the “inner cell mass” ( Figure 1 ). Those pluripotent cells can be isolated, then cultured on a layer of “feeder” cells which provide unknown cues for many rounds of proliferation while sustaining their pluripotency.

Recently, two different groups of scientists induced adult cells back into the pluripotent state by molecular manipulation to yield “induced pluripotent stem cells” (iPS) that share some of the same characteristics as embryonic stem cells such as proliferation, morphology and gene expression (in the form of distinct surface markers and proteins being expressed). 4 - 8 Both groups used retroviruses to carry genes for transcription factors into the adult cells. These genes are transcribed and translated into proteins that regulate the expression of other genes designed to reprogram the adult nucleus back into its embryonic state. Both introduced the embryonic transcription factors known as Sox2 and Oct4. One group also added Klf4 and c-Myc 4 , and the other group added Lin28 and Nanog. 6 Other combinations of factors would probably also work, but, unfortunately, neither the retroviral carrier method nor the use of the oncogenic transcription factor c-Myc are likely to be approved for human therapy. Consequently, a purely chemical approach to deliver genes into the cells, and safer transcription factors are being tried. Results of these experiments look promising. 9

Multipotent

Multipotent stem cells may be a viable option for clinical use. These cells have the plasticity to become all the progenitor cells for a particular germ layer or can be restricted to become only one or two specialized cell types of a particular tissue. The multipotent stem cells with the highest differentiating potential are found in the developing embryo during gastrulation (day 14-15 in humans, day 6.5-7 in mice). These cells give rise to all cells of their particular germ layer, thus, they still have flexibility in their differentiation capacity. They are not pluripotent stem cells because they have lost the ability to become cells of all three germ layers ( Figure 1 ). On the low end of the plasticity spectrum are the unipotent cells that can become only one specialized cell type such as skin stem cells or muscle stem cells. These stem cells are typically found within their organ and although their differentiation capacity is restricted, these limited progenitor cells play a vital role in maintaining tissue integrity by replenishing aging or injured cells. There are many other sub-types of multipotent stem cells occupying a range of differentiation capacities. For example, multipotent cells derived from the mesoderm of the gastrula undergo a differentiation step limiting them to muscle and connective tissue; however, further differentiation results in increased specialization towards only connective tissue and so on until the cells can give rise to only cartilage or only bone.

Multipotent stem cells found in bone marrow are best known, because these have been used therapeutically since the 1960’s 10 (their potential will be discussed in greater detail in a later section). Recent research has found new sources for multipotent stem cells of greater plasticity such as the placenta and umbilical cord blood. 11 Further, the heart, until recently considered void of stem cells, is now known to contain stem cells with the potential to become cardiac myocytes. 12 Similarly, neuro-progenitor cells have been found within the brain. 13

The cardiac stem cells are present in such small numbers, that they are difficult to study and their function has not been fully determined. The second review in this series will discuss their potential in greater detail.

Characteristics that Identify Stem Cells

Since Federal funding for human embryonic stem cells is restricted in the United States, many scientists use the mouse model instead. Besides their ability to self-renew indefinitely and differentiate into cell types of all three germ layers, murine and human pluripotent stem cells have much in common. It should not be surprising that so many pluripotency traits are conserved between species given the shared genomic sequences and intra-cellular structure in mammals. Both mouse and human cells proliferate indefinitely in culture, have a high nucleus to cytoplasm ratio, need the support of growth factors derived from other live cells, and display similar surface antigens, transcription factors and enzymatic activity (i.e. high alkaline phosphatase activity). 14 However, differences between mouse and human pluripotent cells, while subtle, are very important. Although the transcription factors mentioned above to induce pluripotency from adult cells (Oct3/4 and Sox2) are shared, the extracellular signals needed to regulate them differ. Mouse embryonic stem cells need the leukemia inhibitory factor and bone morphogenic proteins while human require the signaling proteins Noggin and Wnt for sustained pluripotency. 15 Surface markers used to identify pluripotent cells also differ slightly between the two species as seen in the variants of the adhesion molecule SSEA (SSEA-1 in mouse, SSEA-3 & 4 in humans). 16 Thus, while pluripotency research in mouse cells is valuable, a direct correlation to the human therapy is not likely.

Last, but certainly not least, a big difference between mouse and human stem cells are the moral and ethical dilemmas that accompany the research. Some people consider working with human embryonic stem cells to be ethically problematic while very few people have reservations on working with the mouse models. However, given the biological differences between human and mouse cells, most scientists believe that data relevant for human therapy will be missed by working only on rodents.

Cell surface markers are typically also used to identify multipotent stem cells. For example, mesenchymal stem cells can be purified from the whole bone marrow aspirate by eliminating cells that express markers of committed cell types, a step referred to as lineage negative enrichment, and then further separating the cells that express the sca-1 and c-Kit surface markers signifying mesenchymal stem cells. Both the lineage negative enrichment step and the sca-1/c-Kit isolation can be achieved by using flow cytometry and is discussed in further detail in the following review. The c-Kit surface marker also is used to distinguish the recently discovered cardiac stem cells from the rest of the myocardium. A great deal of recent work in cardiovascular research has centered on trying to find which markers indicate early multipotent cells that will give rise to pre-cardiac myocytes. Cells with the specific mesodermal marker, Kdr, give rise to the progenitor cells of the cardiovascular system including contracting cardiac myocytes, endothelial cells and vascular smooth muscle cells and are therefore considered to be the earliest cells with specification towards the cardiovascular lineage. 17 Cells at this early stage still proliferate readily and yet are destined to become cells of the cardiovascular system and so may be of great value therapeutically.

Differentiation

Scientists are still struggling to reliably direct differentiation of stem cells into specific cell types. They have used a virtual alphabet soup of incubation factors toward that end (including trying a variety of growth factors, chemicals and complex substrates on which the cells are grown), with, so far, only moderate success. As an example of this complexity, one such approach to achieve differentiation towards cardiac myocytes is to use the chemical activin A and the growth factor BMP-4. When these two factors are administered to pluripotent stem cells in a strictly controlled manner, both in concentration and temporally, increased efficiency is seen in differentiation towards cardiac myocytes, but still, only 30% of cells can be expected to become cardiac. 18

Multipotent cells have also been used as the starting point for cell therapy, again with cocktails of growth factors and/or chemicals to induce differentiation toward a specific, desired lineage. Some recipes are simple, such as the use of retinoic acid to induce mesenchymal stem cells into neuronal cells, 19 or transforming growth factor-β to make bone marrow-derived stem cells express cardiac myocyte markers. 20 Others are complicated or ill-defined such as addition of the unknown factors secreted by cells in culture. Physical as well as chemical cues cause differentiation of stem cells. Simply altering the stiffness of the substrate on which cells are cultured can direct stem cells to neuronal, myogenic or osteogenic lineages. 21 Cells evolve in physical and chemical environments so a combination of both will probably be necessary for optimal differentiation of stem cells. The importance of physical cues in the cell’s environment will be discussed in greater detail in the final review of this series. Ideally, for stem cells to be used therapeutically, efficient, uniform protocols must be established so that cells are a well-controlled and well-defined entity.

Stem Cell Therapy

Pluripotent stem cells.

Pluripotent stem cells have not yet been used therapeutically in humans because many of the early animal studies resulted in the undesirable formation of unusual solid tumors, called teratomas. Teratomas are made of a mix of cell types from all the early germ layers. Later successful animal studies used pluripotent cells modified to a more mature phenotype which limits this proliferative capacity. Cells derived from pluripotent cells have been used to successfully treat animals. For example, animals with diabetes have been treated by the creation of insulin-producing cells responsive to glucose levels. Also, animals with acute spinal cord injury or visual impairment have been treated by creation of new myelinated neurons or retinal epithelial cells, respectively. Commercial companies are currently in negotiations with the FDA regarding the possibility of advancing to human trials. Other animal studies have been conducted to treat several maladies such as Parkinson’s disease, muscular dystrophy and heart failure. 18 , 22 , 23

Scientists hope that stem cell therapy can improve cardiac function by integration of newly formed beating cardiac myocytes into the myocardium to produce greater force. Patches of cardiac myocytes derived from human embryonic stem cells can form viable human myocardium after transplantation into animals, 24 with some showing evidence of electrical integration. 25 , 26 Damaged rodent hearts showed slightly improved cardiac function after injection of cardiac myocytes derived from human embryonic stem cells. 21 The mechanisms for the gain in function are not fully understood but it may be only partially due to direct integration of new beating heart cells. It is more likely due to paracrine effects that benefit other existing heart cells (see next review).

Multipotent stem cells

Multipotent stem cells harvested from bone marrow have been used since the 1960’s to treat leukemia, myeloma and lymphoma. Since cells there give rise to lymphocytes, megakaryocytes and erythrocytes, the value of these cells is easily understood in treating blood cancers. Recently, some progress has been reported in the use of cells derived from bone marrow to treat other diseases. For example, the ability to form whole joints in mouse models 27 has been achieved starting with mesenchymal stem cells that give rise to bone and cartilage. In the near future multipotent stem cells are likely to benefit many other diseases and clinical conditions. Bone marrow-derived stem cells are in clinical trials to remedy heart ailments. This is discussed in detail in the next review of this series.

Pluripotent vs. Multipotent

Pluripotent and multipotent stem cells have their respective advantages and disadvantages. The capacity of pluripotent cells to become any cell type is an obvious therapeutic advantage over their multipotent kin. Theoretically, they could be used to treat diseased or aging tissues in which multipotent stem cells are insufficient. Also, pluripotent stem cells proliferate more rapidly so can yield higher numbers of useful cells. However, use of donor pluripotent stem cells would require immune suppressive drugs for the duration of the graft 28 while use of autologous multipotent stem cells (stem cells from ones’ self) would not. This ability to use one’s own cells is a great advantage of multipotent stem cells. The immune system recognizes specific surface proteins on cells/objects that tell them whether the cell is from the host and is healthy. Autologous, multipotent stem cells have the patient’s specific surface proteins that allow it to be accepted by the host’s immune system and avoid an immunological reaction. Pluripotent stem cells, on the other hand, are not from the host and therefore, lack the proper signals required to stave off rejection from the immune system. Research is ongoing trying to limit the immune response caused by pluripotent cells and is one possible advantage that iPS cells may have.

The promises of cures for human ailments by stem cells have been much touted but many obstacles must still be overcome. First, more human pluripotent and multipotent cell research is needed since stem cell biology differs in mice and men. Second, the common feature of unlimited cell division shared by cancer cells and pluripotent stem cells must be better understood in order to avoid cancer formation. Third, the ability to acquire large numbers of the right cells at the right stage of differentiation must be mastered. Fourth, specific protocols must be developed to enhance production, survival and integration of transplanted cells. Finally, clinical trials must be completed to assure safety and efficacy of the stem cell therapy. When it comes to stem cells, knowing they exist is a long way from using them therapeutically.

Acknowledgments

Supported by NIH (HL 62426 and T32 HL 007692)

[An introduction to stem cell research]

Affiliation.

1 Reproduktionsbiologisk Laboratorium, Rigshospitalet, Juliane Marie Centret, 2100 København Ø, Denmark.
PMID: 20920401

Stem cells (SC) are characterized by the ability of self renewal as well as specialization into different cell types. Stem cells are present in most organs, and can be isolated from adult tissue, embryonic tissue and can be created by a new technology named induced pluripotency. The three types of SC have different potentials in terms of advancing regenerative medicine, but also raise serious safety concerns that need to be addressed before SC can fulfill the expectations by being developed into new cures and treatments for a range of serious cell degenerative diseases.

Publication types

English Abstract
Adult Stem Cells / physiology
Biomedical Research*
Embryonic Stem Cells / physiology
Pluripotent Stem Cells / physiology
Regenerative Medicine*
Stem Cell Transplantation
Stem Cells* / physiology

Stem Cell Research Essay: Research Ethics, Pros and Cons, and Benefits

Stem cell research essay: introduction, why are stem cells useful, stem cell research ethics: pros and cons, how does stem cell research benefit society, embryonic stem cell research essay: conclusion.

Bibliography

Stem cells are capable of regenerating any tissue and organs in the body. Why are stem cells useful? They are characteristically pluripotent, which allows them to replenish damaged body tissues. In an adult human, bone marrow cells have the ability to divide constantly to replenish dying blood cells.

Pluripotency allows embryonic cells to “divide continuously to giving rise to differentiated tissues and organs” [1]. They also produce replacements for cells that are lost through normal wear and tear, injury, or disease [2]. While embryonic stem cells develop from pre-implantation embryos and are pluripotent, adult stem cells occur in fetal and adult stages [3]. In the human body, adult stem cells function in the repair and replacement of worn-out tissues. This stem cell research argumentative essay will analyze stem cell research ethics’ pros and cons and explain how it can benefit society.

Stem cell research has potential benefits in the treatment of chronic diseases. Stem cell therapy has shown promising results in the treatment of leukemias and blood and bone marrow disorders[4]. Current research focuses on developing stem cell therapy for heart disease, Parkinson’s disease, diabetes mellitus, amyotrophic lateral sclerosis, and arthritis.

Fetal surgery for the treatment of patients with congenital anatomical abnormalities such as myelomeningocele is also a promising area of stem cell research[5].

Cell replacement therapy for neurodegenerative defects, such as multiple sclerosis, have been found to offer long-term physiological benefits, making it a better alternative to conventional drug therapy[6]. Stem cells are also useful in drug research and development. Cell lines from carriers of genetic diseases are used to model the disorders and test potential, thus, speeding up the drug trial process.

Ethical perspectives aim to identify principles of right action that can guide society in thinking about moral decisions or how to navigate through dilemmas[7]. In this respect, though scientific research is essential in solving contemporary problems facing humans, it must be done within the confines of ethical conduct[8].

In stem cell research, several ethical issues dominate public debates. In particular, the issues of right to life at the fetal stage and the criteria for disseminating medical breakthroughs remain contentious. Another issue relates to the risks versus the benefits of research involving embryonic cells.

The moral debate also revolves around the rights of fetuses and issues of consent. The challenge lies in determining whether it is moral to harvest cells from a human fetus for scientific research. Proponents advance the argument that a fetus at an early stage of life is underdeveloped, and therefore, does not have the attributes of an adult or a young child[9].

They argue that it has no resemblance to a human being, has nobody organs and organ systems, and lacks self-awareness. However, critics contend that it is unethical to utilize embryonic cells for research as doing so contravenes the dignity of the unborn child.

They also hold that all humans share common attributes, and thus, claiming that embryos lack sentience is erroneous[10]. Their argument relates to the embryology perspective, which holds that “human life begins at fertilization” [11]. Therefore, embryos, being human beings at an early stage of development, cannot be used in scientific research.

In contrast, proponents of stem cell research fault the embryology perspective by arguing that research on embryos is ethical, as evidenced in identical twins that develop from the splitting of an early embryo. They pose the question: “If life begins at conception, then when does the life start for the twins?” They reckon that humans, being moral beings, cannot be equated with animals[12].

Thus, while research on animals may be permissible, the same cannot be said about humans what humans identify as the self is not the body, but the conscious. In this view, humans do not exist until they develop consciousness, and therefore, the destruction of the embryos for research cannot be morally wrong[13]. In this regard, participating patients must give informed consent prior to the use of embryonic cells sourced from unborn fetuses[14].

The ethical implications of the techniques used for obtaining stem cells have also borne on the actions of scientists and the decisions of policymakers. Another good source of pluripotent cells for research is stillborn fetuses or adults.

This procedure is less controversial, the only ethical issue being the acquisition of proper donor consent. Patients carrying cancerous embryos can donate them for research since the fetus will not survive upon birth[15]. The scientific and ethical concern presented by this approach concerns the potential of induction of tumorigenesis in recipients.

In vitro fertilization often generates test tube zygotes ready for uterine implantation. However, unsuccessfully implanted zygotes can be used for scientific research if the parents consent. This procedure involves the destruction of the embryo and is not acceptable to those who believe human embryos have a moral status similar to that of adult human beings.

However, in vitro, fertilization yields many fetuses to increase the chances of successful implantation[16]. Atsuo raises serious ethical concerns over the creation of more than one embryo through the IVF procedure[17].

He holds that it is both unlawful and unethical to do artificial fertilization to generate embryos for research. In non-destructive embryo cell extraction, a single cell or a small number of cells is extracted from an early-stage embryo. These cells have the potential to divide and give rise to a line of embryonic stem cells[18].

Embryonic stem cells can also be obtained from dead embryos, i.e., embryos that have stopped dividing. The ethical question posed with this procedure is how certain one can be that the embryo is dead since death is the failure of important organs like the heart and the brain, which the embryo does not have[19].

Critics also argue that doctors may misuse in vitro fertilization, creating excess fetuses for sterile couples. Thus, in vitro fertilization done for generating embryos for science is unethical and unlawful.

In the debate on embryo research, two perspectives are evident, namely, a ‘fetalist’ perspective and a feminist perspective. Proponents of the ‘fetalist’ view argue that fetuses have rights, and thus, research-based on embryonic cells dehumanizes them.

It makes fetuses mere objects of scientific research. In contrast, the feminist perspective focuses on the interests of women who donate the oocyte[20]. Normally, in the IVF procedure, female patients receive drugs to stimulate the required hormonal balance and increase the chances of implantation. In addition, the perspective considers the moral justification related to the treatments.

It is evident that stem cells have great potential as therapeutic agents for chronic human diseases, including cancer and heart disease. They can divide to generate new tissue that can then be transplanted into the patient to remedy a disease condition or disorder.

In this view, proponents contend that promoting this kind of research will lead to several medical breakthroughs beneficial to humans. In addition, they note that research on embryonic cells will enrich our basic scientific knowledge. The pursuit of scientific knowledge, though a valuable undertaking, runs the risk of being abused in the future by researchers interested in unethical projects, such as human cloning.

Stem cell therapy presents some advantages in that it makes transplantation a success as reprogrammed adult cells are rarely rejected[21]. In addition, the ability to grow embryonic stem cells helps to generate more stem cells for research, thus circumventing the task of frequent isolation from embryos. With stem cell research, the histo-compatibility barrier is avoided, especially with the use of IPS cells[22].

Stem cell therapy has potential as a remedy for congenital abnormalities. One such chronic disorder is multiple sclerosis, which defies conventional interventions. In this respect, the research can create an effective therapy to help patients with birth defects lead to a normal life.

In addition, disorders caused by hormonal deficiency can be treated with organ transplantation. Pluripotent cells, under the right conditions, can generate new tissues and organs with potential as transplants. Therefore, the therapeutic benefits of research based on embryonic cells are immense.

Looking at the benefits and shortcomings presented by stem cell research, one is left in a dilemma whether to support it or advocate for its discontinuity. Individuals are torn between respecting the sanctity of human life or alleviating the suffering of many sick people through stem cell therapy.

The benefits accruing from stem cell research are immense and indispensable. With proper regulations, policies, and scrutiny, they can be harnessed to improve the health of the sick people.

[1] James, Bobrow, “The Ethics and Politics of Stem Cell Research,” Transactions of the American Ophthalmological Society 104 (2005): 139.

[2] Bobrow, “The Ethics and Politics of Stem Cell Research,” 140.

[3] Connie Witherspoon, “Ethical Considerations Regarding Stem Cell Research,” The New Atlantis 1(2012): 98.

[4] Witherspoon, “Ethical Considerations Regarding Stem Cell Research,” 100

[5] Witherspoon, “Ethical Considerations Regarding Stem Cell Research,” 105

[6] Witherspoon, “Ethical Considerations Regarding Stem Cell Research,” 108

[7] Montague Shelby. “Stem Cell Research: The Ethical Issues,” The Yale Journal of Biology and Medicine 82 (2009): 125.

[8] Shelby, “Stem Cell Research,” 127.

[9] Shelby, “Stem Cell Research,” 125.

[10] Shelby, “Stem Cell Research,” 126.

[11] Shelby, “Stem Cell Research,” 126.

[12] Guido De Wert and Christine Mummery, “Human Embryonic Stem Cells: Research, Ethics and Policy,” Oxford Journals 18 (2015): 672.

[13] De Wert and Mummery, “Human Embryonic Stem Cells,” 674.

[14] Shelby, “Stem Cell Research,” 127

[15] De Wert and Mummery, “Human Embryonic Stem Cells,” 674.

[16] Ogura Atsuo, “Recent Advancements in Cloning by Somatic Cell Nuclear Transfer,” The Royal Society Publishing 138 (2012): 1.

[17] Ogura Atsuo, “Recent Advancements in Cloning by Somatic Cell Nuclear Transfer,” 2.

[18] Shelby, “Stem Cell Research,” 127

[19] Shelby, “Stem Cell Research,” 127

[20] Ogura Atsuo, “Recent Advancements in Cloning by Somatic Cell Nuclear Transfer,” 2.

[21] Deborah White, “Pros & Cons of Embryonic Stem Cell Research,” Stem Cell Research News 1 (2015): 1.

[22] Deborah White, “Pros & Cons of Embryonic Stem Cell Research,” 2.

Atsuo, Ogura. “Recent Advancements in Cloning by Somatic Cell Nuclear Transfer.” The Royal Society Publishing 138 (2012): 1-2.

Bobrow, James. “The Ethics and Politics of Stem Cell Research.” Transactions of the American Ophthalmological Society 104 (2005): 138-42.

De Wert, Guido, and Christine Mummery. “Human Embryonic Stem Cells: Research, Ethics and Policy.” Oxford Journals 18 (2015): 672-682.

Shelby, Montague. “Stem Cell Research: The Ethical Issues.” The Yale Journal of Biology and Medicine 82 (2009): 125-131.

White, Deborah. “Pros & Cons of Embryonic Stem Cell Research.” Stem Cell Research News 1 (2015): 1-4.

Witherspoon, Connie. “Ethical Considerations Regarding Stem Cell Research.” The New Atlantis 1 (2012): 98-113.

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Sample essay on stem cell research: a historical and scientific overview.

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Stem cell research is one of the important scientific and political issues of these modern times. The purpose of this sample essay, one of the many writing services offered by Ultius , is to develop a historical and scientific overview of this selected issue. The essay will begin with a general introduction to stem cell research. Then, it will discuss the scientific history of stem cell research as it has unfolded over the past several years; and after this, it will turn to a consideration of the political history of stem cell research. Finally, it will provide a summary reflection on contemporary debates and conflicts that are currently surrounding the issue of stem cell research. This type of document would likely be required in a mid-level English or science course where the focus is on general education over specialized study.

Introduction to Stem Cell Research

According to the American Medical Association:

"[A] stem cell is an immature cell that has the potential to become specialized into different types of cells throughout the body the body," and "there are two basic types of stem cells: adult stem cells and embryonic stem cells" (paragraphs 1-2).

Adult stem cells can actually be found in both adults and children. Their name comes from the fact that they can be harvested from mature tissue without causing harm to the person from whom they are harvested. Embryonic stem cells, on the other hand, can only be derived from embryos, and the harvesting process destroys the embryos. From this basic introduction, it is already clear that embryonic stem cell research has far greater potential to be ethically problematic than adult stem cell research. However, embryonic stem cell research is also generally considered to have the greatest potential for delivering medical and scientific breakthroughs, due to the fact that they are even more flexible (so to speak) and undifferentiated than adult stem cells (see Bongo and Richards).

Benefits of stem cell research

From the medical perspective, stem cell research is viewed as very promising due to the fact that if stem cells can be introduced into patients with a range of illnesses, they could possible help regenerate the tissues and organs of the patients and thereby help heal illnesses (and especially degenerative illnesses) that are currently incurable. For example, Lovell-Badge has indicated that diabetes, Parkinson's disease, and Huntington's disease are among the illnesses that could potentially be responsive to stem cell research (88). Again, given that the potential of stem cell research is directly correlated with the plasticity of the stem cells in question, it logically follows that there will be an increasing push by scientists to focus research on embryonic stem cells if at all possible, due to the fact that they have greater plasticity than adult stem cells and thus greater potential to contribute to medical breakthroughs. The moral dimension of the issue, however, has generally led to limitations being imposed on the capacity of scientists to pursue embryonic stem cell research.

Scientific history of stem cell research

The organization Science Progress has provided a good summary of some of the main events that have marked the scientific history of stem cell research. These include:

The first isolation of stem cells from mice in the year 1980
The first isolation in primates in the year 1995
The first isolation in humans in the year 1997

These events were important due to the fact that scientifically speaking, the isolation of stem cells from other elements within the body would be a prerequisite for conducting rigorous research on stem cells themselves. From this point, human scientific history over the course of the last decade and a half has been characterized by progressive breakthroughs in stem cell technologies, including:

Stem cell transplants for patients with illnesses such as leukemia
Trials with human beings with degeneration of the eyes
Experiments with mice regarding the regeneration of heart tissue
The cloning of embryonic stem cells (which would avert the need to harvest new stem cells from new embryos)

Clearly, the scientific progress over the past several years gives great cause for hope. There has been a steady trend of scientists increasingly learning the secrets of stem cells and being able to apply their new knowledge to either research potential treatments or actually deliver effective treatments to human beings. Therefore, it could be suggested that anyone who has a real interest in seeing major medical breakthroughs happen (which, presumably, would be almost everyone) cannot afford to oppose the ongoing development of stem cell research per se. What there clearly can be controversy over, though, is how exactly the research agenda ought to proceed. In order to more effectively address this dimension of the issue presently under consideration, it may be a good idea to turn now to the political history of stem cell research, or legislation that has surrounding the issue as it has developed over time.

Political history of stem cell research

One of the clearest points that emerges regarding the political history of stem cell research and bioengineering in general , is that there has been ongoing controversy over the extent to which the federal government should fund research. This has proved to be a quite partisan issue. For example, in 2001, Bush issued an executive order that placed significant restrictions on federal funding for stem cell research; and in 2009, Obama countermanded this order with an order of his own called "Removing Barriers to Responsible Scientific Research involving Human Stem Cells" (see Research America). This, of course, is tied to broader political conflicts regarding issues such as religion and abortion. If the federal government is to spend tax money on stem cell research, then this would likely contradict the values of many Americans, and especially conservative Americans, regarding the origins of human life. This is likely why the main legislative barriers against stem cell research have always focused on embryonic stem cell research. Again, as has been noted above, significantly greater ethical dilemmas inhere to research with embryonic stem cells than to research with adult stem cells.

Restrictions on stem cell harvesting

A good example of such restrictions can be seen in the guidelines for stem cell research released by the National Institute of Health in 2000, which stipulated that:

"human embryonic stem cells must be derived with private funds from frozen embryos from fertility clinics; that they must have been created for fertility treatment purposes; that they be in excess of the donor's need; and that they be obtained with consent of the doctor" (Research America, 25 Aug. 2000 entry).

Several important ethical points are exemplified by this statement, including that embryonic stem cells must be derived using private (and not public) funds and that it still is not acceptable to create embryos simply for the sake of harvesting stem cells from them (and destroying them in the process). Over the course of the last several years, though, such regulations would seem to have become someone less salient both due to their relaxation under the Obama administration and to scientific innovations regarding adult stem cells, which have enabled scientists to somewhat circumvent the legislative debate surrounding embryonic stem cells.

Summary of current situation

As Wertz has succinctly put it:

"stem cell research in the United States is inevitably connected with the politics of abortion " (674).

This is because controversy over stem cell research generally tends to focus on the use of embryonic stem cells; but then, this leads to the more fundamental question of the legal, ethical, and metaphysical status of the embryo. In principle, if one grants that abortions are acceptable, then one must also grant that it is acceptable to create embryos specifically for the purpose of harvesting stem cells from them. This logically follows because abortion could only be deemed acceptable if the embryo is not considered to be alive and/or metaphysically human; and if this were the case, then there would be no moral grounds for opposing the manufacture of embryos for the purposes of stem cell research. To put it a little differently: insofar as an embryo is not understood as a living human being, there would be no reason for controversy to even arise regarding this matter.

When does life begin?

Of course, there is a significant number of Americans who believe that life begins at conception, and that the embryo is thus in fact metaphysically a living human being. If this were the case, then the manufacture of embryos simply for the purpose of destroying them would be horrific, insofar the destruction of each embryo would then be morally and conceptually equivalent to murder. If this paradigm is accepted, then whatever benefits could be produced by embryonic stem cell research would clearly be outweighed by unacceptability of the atrocities that would need to be committed in order to achieve those benefits.

Clearly, this conflict ultimately surpasses the bounds of science itself and is grounded in the differing religions and broader worldviews of different groups of people within the nation. As Robertson has written:

"There is a fervent battle over the ethical acceptability of destroying early embryos . . . Stem cell science is thus drawn into the ongoing, highly divisive wars over abortion and the culture of life that have occupied a central stage in American law and politics over the last 30 years" (192).

Stem cell research is thus a highly partisan issue, and it is likely to remain that way over the foreseeable future. Again, this is because the real points of contention that surround the issue surpass the scope of science or even reason more generally; they touch on people's fundamental beliefs about what it means to be human. For example:

One side may argue that embryos are not humans and that it is thus acceptable to destroy them in order to relieve the suffering of actual humans
The other side may argue that embryos are in fact humans and that under no circumstances can their destruction be acceptable

Both positions would be cogent within the context of their own assumptions; and it would be difficult if not impossible to rationally discredit either set of assumptions.

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The power of god?

In addition, it is worth pointing out that even adult stem cell research is controversial, insofar as stem cell research in general has the potential to lead to human cloning . The basic point here would be that human beings are engaging with a dangerous power that may be intimately connected with the very origins of life itself. Again, whether this is problematic would depend entirely on one's religion and/or broader worldview. If there were no God, then there would naturally be no problem with human beings pushing their knowledge to the limits. On the other hand, if one did believe in God, then it would be possible to argue that stem cell research is an attempt by humans to usurp His role. As with the morality of the destruction of embryos, this question can be expected to remain open for a quite long time.

In summary, this essay has provided a historical and scientific overview of the issue of stem cell research . It began with an introduction to the issue, proceeded to discuss the scientific and political history of the issue, and finally reflected on the current situation regarding the issue. One of the main points that has emerged here and throughout research paper writing on the subject is that although stem cell research clearly has a great deal of potential for catalyzing medical breakthroughs, the research agenda has been limited to at least some extent by legislative barriers based on moral concerns. Given the nature of the issue at hand, these latter concerns clearly are not irrelevant. Moreover, it could even be suggested that without the barriers, certain recent scientific innovations (such as those pertaining to adult stem cells) may not have come about. In general, then, it is perhaps a good idea for stem cell research to proceed in the cautious and pragmatic way that it has thus far.

Works Cited

American Medical Association. "Basics of Stem Cell Research." n.d. Web. 20 Dec. 2014. <http://www.ama-assn.org/ama/pub/physician-resources/medical-science/genetics-molecular-medicine/related-policy-topics/stem-cell-research/basics-stem-cell-research.page?>.

Bongso, Ariff, and Mark Richards. "History and Perspective of Stem Cell Research." Best Practice & Research Clinical Obstetrics and Gynaecology 18.6 (2004): 827-842. Web. 19 Dec. 2014. <http://www.ualberta.ca/~dcl3/Stem%20Cell%20Reviews/review_SC+history+basics+of+rsch.pdf>.

Lovell-Badge, Robin. "Overview: The Future for Stem Cell Research." Nature 414 (2001): 88-91. Print.

Research America. "Timeline of Major Events in Stem Cell Research Policy." 2014. Web. 20 Dec. 2014. <http://www.researchamerica.org/timeline>.

Robertson, John A. "Embryo Stem Cell Research: Ten Years of Controversy." Journal of Law, Medicine & Ethics (Summer 2010): 191-203. Web. 20 Dec. 2014. <http://www.utexas.edu/law/faculty/jrobertson/JLME-10-year-survery-Robertson-final.pdf>.

Science Progress. "Timeline: A Brief History of Stem Cell Research." 16 Jan. 2009. Web. 20 Dec. 2014. <http://scienceprogress.org/2009/01/timeline-a-brief-history-of-stem-cell-research/>.

Wertz, D. C. "Embryo and Stem Cell Research in the United States: History and Politics." Gene Therapy 9.11 (2002): 674-678. Web. 19 Dec. 2014. <http://www.nature.com/gt/journal/v9/n11/full/3301744a.html>.

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Embryonic Cells in Stem Cell Research Essay

Introduction, works cited.

Stem cell research (SCR) has been the subject of many controversies over the past few decades. Studies have shown that the exploration of the options that SCR provides may lead to the creation of the cure for diseases such as cardiovascular (CVD) health issues, Parkinson’s disease, Alzheimer’s disease, and diabetes, to name just a few (Zhang et al. 85). Therefore, despite possible ethical concerns associated with the implications of SCR on human nature, I believe that the use of embryonic cells as one of the key aspects of CSR should be promoted as a possible source for solutions for numerous diseases and disorders.

The use of embryo cells in SCR opens various possibilities for addressing some of the most complex health issues, which means that the research has to be supported. SCR, in general, and the use of embryonic cells, in particular, are likely to have huge positive implications for healthcare and the management of diseases such as CVD, Parkinson’s, and Alzheimer’s (“Chapter 9 – Cell Communication”). Although the opponents of SCR may claim that it implies playing God and tampering with human nature, the positive outcomes that SCR may have should be explored and used to their full potential.

Due to the potential in managing the diseases and disorders that are presently deemed as incurable, I am certain that CSR should be continued despite the ethical concerns that it raises. Since the possible positive outcomes outweigh the ostensible negative implications, the research should continue, with a greater focus on the treatment opportunities that the utilization of embryonic cells provides. Despite the fact that the use of the specified material may be seen as challenging to the concept of morality and the current social norms, the treatment opportunities that it potentially has been tremendous. Thus, the opportunity described above should not be missed.

“Chapter 9 – Cell Communication.” Georgia Highlands College , n.d. Web.

Zhang, Qingxi, et al. “Stem Cells for Modeling and Therapy of Parkinson’s Disease.” Human Gene Therapy , vol. 28, no. 1, 2017, pp. 85-98.

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Free Stem Cells Research Paper Example

Type of paper: Research Paper

Topic: Health , Adulthood , Medicine , Development , Nursing , Adult , Leukemia , Skin

Words: 1700

Published: 02/26/2020

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This paper describes and discusses the various types of human stem cells, including those in early-stage embryos (the blastocyst) and those present in adult tissue, explaining the practical uses of the various types in the medical field, where stem cells can be used to repair damaged tissue and organs. Although the adult stem cell types offer fewer possibilities for medical applications than the embryonic type, their use is less ethically controversial because it does not require destruction of a living albeit very early stage embryo. Research into stem cell applications is finding improved techniques. These include the treatment of acute leukemia that was once a fatal disease but is increasingly treatable using stem cell therapy in the form of bone marrow transplants, progressively increasing the survival rates for leukemia patients. In conclusion it is recommended that because stem cell technology and therapy is potentially so important for future treatment of diseases, such research should not only be continued but expanded in scope. Stem Cells

Introduction

This paper discusses and researches the various types of stem cells, the research in hand to use them to treat leukemia and the prognosis for greater probability of survival by regenerating a damaged immune system.

What Are Stem Cells?

An easily understood explanation of stem cells is provided in “Definition: What are Stem Cells?” (2007) published by the University of Minnesota (UMN). They are defined as human cells that are “blank”, meaning that they can potentially develop into any of the many specialized cell types which comprise the majority of the cells in the human body. Those specialized or differentiated cells are different to the stem cells which are undifferentiated. Examples of differentiated cells are red blood cells which are designed to hold and transport oxygen, and a white blood cell which is specially equipped to fight off disease.

Stem Cell Types

The UMN article explains that there are two basic types of stem cells, known either as Pluripotent or Multipotent. The Pluripotent stem cell type is found in early-stage embryos and can develop into all the cell types present in the human body; these may include cells found in organs such as the brain or heart and in bone and skin tissue. The Multipotent stem cells are found only in adults or in the umbilical cords of newborn babies. Their capacity for development is more limited, in that they can only develop into cells comprising the organ system that they came from. Hence one such cell from bone marrow can only develop into one of three types: a red or white blood cell or a blood platelet. It cannot develop into other types such as a brain cell or skin tissue cell. In addition to those two basic types of stem cells, there is a third type known as Induced Pluripotent stem cells or IPSCs (alternative name reprogrammed stem cells). According to Cox (Aug. 2012), these are similar to the embryonic or Pluripotent type found in early stage embryos, but are in fact created from adult (specialized) cells in the laboratory, using a technique discovered as recently as 2006. Further, there are three other “potency” classifications of stem cells as described by Crosta (2008-2013). These are Totipotent – having the ability to different into every possible cell type (cells from the earliest few divisions after fertilization), Oligopotent – cells able to differentiate into a few other cells (e.g. adult lymphoid or myeloid stem cells); and Unipotent – cells that can only differentiate into the same type (e.g. adult muscle stem cells). An important aspect of the 2006 discovery is that whereas stem cell research using cells extracted from embryos is the subject of considerable controversy because it effectively involves destroying an embryo that has been artificially fertilized at 5-14 days (“Definition: What are Stem Cells?, 2007), research using IPSCs is not so controversial. Note that the research usually uses “extra” embryos that have been created in an in vitro fertilization (IVF) clinic, following the implantation of one embryo in the woman subject (Crosta, 2008-2013). As explained by Crosta, those very early stage embryos (4 to 5 days) begin as a single cell called a zygote at fertilization. It then goes through a series of divisions (first 2, then 4, then 8, then 16, etc) and this developing cell mass is referred to at this stage as a blastocyst. It comprises an inner mass (embryoblast), which would normally go on to grow into a complete adult organism, and an outer mass (trophoblast) which would develop as the placenta. It is that inner mass from which stem cells can be harvested by placing it in culture dish. Those stem cells then divide and replicate themselves as undifferentiated cells Part of the reason why using adult stem cells does not attract the same controversy is that adult (or stomatic) stem cells exist in all of our bodies following embryonic development and can be found in the different human tissues types – in organs like the brain and the liver, and in bone marrow, blood and blood vessels, muscular tissue and the skin (Crosta). A characteristic feature of these stem cells is that they remain in a non-dividing condition unless activated due to a disease or an injury to the host. Also, they are able to divide and/or renew themselves indefinitely, having the ability to create cell types from the organ that contains them, or even to regenerate the complete organ. Whilst there are thoughts that they may have limited differentiation abilities according to the tissue type in which they originated, there are possibilities that they may be able to differentiate and become other cell types, too.

Stem Cell Therapy for Leukemia

“Promising Stem Cell Therapy for Leukemia Patients” (Apr. 2013) describes how stem cell therapy in the form of bone marrow transplants gives today’s leukemia patients a chance of survival that did not exist years ago. Leukemia is a formerly fatal cancer of the blood-building cells in the bone marrow. To deal with the cancerous cells in the bone marrow, patients are given chemotherapy and radiotherapy prior to a bone marrow transplant, which is effectively the beginning of a new immune system. The newly-transplanted cells take over the task of producing healthy blood cells from the diseased ones, at the same time as attacking and destroying the leukemia cells. There are risks involved in that the new immune system comes from outside the patient’s body and can as a consequence also attack healthy patient tissues, a phenomenon called GvHD (Graft versus Host Disease). In severe cases that can cause organ failure. Up to 50 percent of bone marrow transplant patients are affected, and in some 20 percent of those (so 10 percent of the total), the damage caused is fatal. There is also an additional risk that around 20 percent of all leukemia patients can suffer a relapse following the transplant. However, to reduce the risks of GvHD, the physicians treat transplant patients with carefully measured doses of immunosuppressants, so as to suppress the immune system, but not too much, which could cause the attacks on the cancerous cells to be ineffective. Research is in hand to find ways to prevent GvHD, including using antibodies to treat the new cells prior to transplantation so that they will “tolerate” the healthy tissue cells as opposed to attacking them, in this way helping to increase the success rate of the bone marrow transplant procedures. Initial tests have shown the principles to be valid, and testing is currently underway using mice modified with a human immune system, moving on soon to a clinical study. Giebel (Dec. 2013) published encouraging results of a study of autologous bone marrow transplants for 177 patients to treat Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL), showing clear improvements in survival rates following the “introduction of tyrosine kinase inhibitors.” The study showed that the three-year survival rates increased with the more recent transplant dates as follows: 1996 to 2001: 16 percent; 2002 to 2006: 48 percent; 2007 to 2010: 57 percent. Further statistics from the study showed an even higher rate for a selected subgroup of the patients after three years, and that the more recent the transplant date, the better the survival rates have become; i.e. that the research resulting in refining the techniques is continuing to increase the likelihood of survival.

Conclusions and Recommendations

The research undertaken has shown that there are two main types of stem cells: embryonic (or Pluripotent ) and adult tissue (or Multipotent) stem cells, which have fewer development capabilities than the embryonic type. Research over recent years has shown there are potentially exciting possibilities for treating diseases using stem cell therapy, including the possibility of regenerating human organs instead of depending on transplant surgery. Survival rates for acute leukemia patients have increased with increasing knowledge and better techniques in the field of stem cells applications for bone marrow transplants. For that reason this writer recommends continuing and increasing that research to improve the prognosis even further for patients with leukemia, and widening the scope of the present research to develop and improve treatments for other life-threatening diseases, too.

References:

Cox, Claire. (Aug. 2012). “Stem cell research & therapy: types of stem cells and their current uses.” Euro Stem Cell. Retrieved from http://www.eurostemcell.org/factsheet/stem-cell-research-therapy-types-stem-cells-and-their-current-uses Crosta, Peter. (2008-2013). “What are Stem Cells?” Medical News Today. Retrieved from http://www.medicalnewstoday.com/info/stem_cell/ “Definition: What are Stem Cells?” (2007). University of Minnesota: Academic Health Center. Retrieved from http://www.ahc.umn.edu/bioethics/prod/groups/ahc/@pub/@ahc/documents/asset/ahc_75703.pdf Giebel, S. (Dec. 2013). “ASCT improved outcomes in Ph+ALL.” Eur J Cancer. 2013; doi:10.1016/j.ejca.2013.08.027. Retrieved from http://www.healio.com/hematology-oncology/hematologic-malignancies/news/online/%7Bb14f81e4-5e9e-4733-8ef0-29781584c7fe%7D/asct-improved-outcomes-in-phall “Promising Stem Cell Therapy for Leukemia Patients.” (Apr. 2013). Science Daily. Retrieved from http://www.sciencedaily.com/releases/2013/04/130402091248.htm

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Introduction. Stem cell research (SCR) has been the subject of many controversies over the past few decades. Studies have shown that the exploration of the options that SCR provides may lead to the creation of the cure for diseases such as cardiovascular (CVD) health issues, Parkinson's disease, Alzheimer's disease, and diabetes, to name just a few (Zhang et al. 85).
Stem Cells Research Papers Examples
Read Good Research Paper On Stem Cells and other exceptional papers on every subject and topic college can throw at you. ... showing clear improvements in survival rates following the "introduction of tyrosine kinase inhibitors." The study showed that the three-year survival rates increased with the more recent transplant dates as follows ...

Stem Cell Research Benefits

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Stem Cell Research & Therapy

Introduction to Stem Cells

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NIH Stem Cell Information

Introduction to Stem Cell Therapy

Brenda Russell

Introduction

Stem Cell Fates

Sources of Stem Cells

Multipotent

Characteristics that Identify Stem Cells

Differentiation

Stem Cell Therapy

Multipotent stem cells

Pluripotent vs. Multipotent

Acknowledgments

[An introduction to stem cell research]

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Stem Cell Research Essay: Research Ethics, Pros and Cons, and Benefits

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Introduction to Stem Cell Research

Benefits of stem cell research