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Human embryonic stem cells: preclinical perspectives


Human embryonic stem cells (hESCs) have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic.

1. Introduction

Biomedical research using embryonic stem cells (ESC) is a very promising area for the investigation of the possibilities of developing newer cell replacement therapies (CRTs). Diseases and disorders which have no therapy or at best partially effective ones mainly attract the pursuit of ESC research. The first ESC line was established from mouse embryos in 1981 [1], following a method virtually identical to rabbit models used by Cole RJ et al., [2] about 30 years earlier. These ESCs have been used for introducing specific gene modifications in mice. Sir Martin Evans has recently been honored with the Nobel Prize for Physiology and Medicine (2007) for his contribution towards development of animal models of disease through ESC mediated gene targeting. Human embryonic stem cells were first derived by Thompson's group in 1998 [3] and are usually derived from the inner cell mass (ICM) of blastocyst stage embryos that are left over after in vitro fertilization (IVF) and after embryo donations [4]. The derivation of hESCs have opened up huge possibilities for regeneration and repair of organs of tissues and thus been envisioned as therapeutic agents.

"Self-renewal" i.e., the ability to undergo indefinite self-renewing and symmetric cell divisions to maintain the population, and "pluripotency" which indicates their ability to differentiate into any of the 200 different known cell types (of ectoderm, endoderm, mesoderm and trophectoderm lineages); are the two hallmarks of these cells [5]. Though these are the key properties of the hESCs, yet they are not a property of the ICM in vivo and must be a characteristic adopted by the cells during their initial outgrowth in the culture. The use of human embryonic stem cells (hESCs) in cell replacement therapies (CRTs) has been limited due to several technical and ethical issues. Since its inception there has been an extensive debate about the benefits and drawbacks of adult vs hESC use in therapies [6, 7]. For hESCs the problems range from the way they are derived, characterized, established and maintained, to their in-vitro differentiation and transplantation. Changes in their epigenetic profiles, chromosomal aberrations during their establishment and maintenance, post transplantation challenges like risk of tumors, genetic instability, and immune-rejections are some of the other major concerns.

ESC-like cells have also been derived from mouse skin cells [7]. ESC lines have also been established from single cell biopsies of a developing embryo [8, 9]. Such advances if successfully reproduced in human, could possibly demolish the ethical objections related to destroying a potential life that has haunted the field for many years. This review presents a generalized opinion and outlook on the alternative strategies required to develop effective and novel hESCs based therapies.

2. Barriers to bringing hESCs to clinic

Seven major concerns identified as significant roadblocks to the safe transition of hESC to clinic are discussed in the following subsections.

2.1 Derivation of hESCs: need for "Embryo-friendly" ways

Destruction of life in the form of an embryo has been a major ethical objection in embryonic stem cell derivation and research in several western countries. One way to get around this objection will be to generate human ESC lines without the use of additional human embryos. The different approaches suggested so far are discussed below:

a) Reprogramming of adult cell nucleus

The method uses existing hESCs to fuse with an adult somatic cell, generating a cell line that retains ESC specific properties and yet has the genotype of the somatic cell donor [10]. However, there is no technology available to selectively remove all the ESC chromosomes while retaining the somatic cell chromosomes. In addition this removal of chromosome needs to be timed to occur only after the hybrid cell has been reprogrammed to take the properties of the stem cells. Development of such technologies is potentially expensive and will presumably take years.

b) ESCs from embryo like entities

This approach involves the use of somatic cell nuclear transfer (SCNT) to produce developmentally compromised embryo-like structures, with the help of genetically premodified deficient nuclei which cannot support development [11]. The zygote produced by such nuclear transfer undergoes cleavage in-vitro and produce ICM cells, which would be used for deriving ESCs, but would not proceed further in development. A proof of principle to this was accomplished by generating mouse ESCs, using a donor nucleus which was silenced for Cdx2 gene [12]. This is ethically correct for those who believe that fetal life begins only after the embryo implants. However, one need not go for creating a mutation to achieve this target, as a blastocyst cannot develop into a complete human life in vitro, irrespective of the presence or absence of any kind of genetic alterations.

c) ESC lines from single blastomeres

It is known that if a cell or two is missing from a preimplantation embryo it can regenerate the missing part and form a whole embryo. A single cell can be isolated from the cleavage stage embryo, a technique well established for preimplantation genetic diagnosis (PGDs), and used to create a cell line from it; the rest of the embryo can be transferred back to the uterus to give rise to a fetus [8]. Robert Lanza's group has shown that ESC lines could be established from single cell biopsies of the mouse and human embryos [8, 9]. However, this technique is very difficult to translate to human being. Also, the fate of the residual embryos if they are transferred is largely unknown, as there is a lack of long term studies supporting the health of babies born following PGD.

d) ESC lines from induced somatic cell dedifferentiation

In this method the adult somatic cells are genetically modified and reprogrammed to undergo a process of dedifferentiation, by inducing the expression of pluripotency related genes. Recently, induced pluripotent stem cell lines have been derived by allowing trans-acting factors present in the mammalian oocytes to reprogram somatic cell nuclei to an undifferentiated state [13]. They have demonstrated that four factors OCT-4, SOX-2, Nanog and LIN28 are sufficient to reprogram human somatic stem cells to pluripotent stem cells. Whereas, Takahashi and Yamanaka (2006) induced somatic cells into pluripotent stem cells by introducing four factors OCT-4, SOX-2, c-Myc and KLF-4. These cells designated as induced pluripotent stem cells (iPS) exhibit morphology of embryonic stem cells and express ES cell markers [14]. Although, Takahashi and Yamanaka (2006) and Yu et al., (2007) carried out astonishing experiments by reprogramming somatic cells into pluripotent stem cells, several technical limitations such as use of retrovirus or lentiviruses for transfecting OCT-4, Nanog, SOX-2, C-MYC, LIN28 or KLF4 restrict the use of such cell lines for clinical applications [15] (Hanna et al., 2007).

e) Embryonic like stem cells from alternative sources

Adult stem cells similar to blastomeres of the preimplantation stage embryos have been identified and isolated by Henry Young and coworkers [16]. These cells called the blastomere-like stem cells (BLSCs) are found to be totipotent due to their potential to give rise to all tissue types including the gametes. These BLSCs can be induced to differentiate in a unidirectional manner to form pluripotent embryonic-like stem cells (ELSCs). It is also claimed that these cells do not express the MHC class-I or HLA DR-II cell surface markers. More recently Meng et al., (2007) have discovered a population of stem cells in the menstrual blood [17]. These cells named as the "Emdometrial Regenerative Cells" are shown to be capable of differentiating into 9 tissue lineages namely: cadiomyocytic, respiratory epithelial, neurocytic, myocytic, endothelial, pancreatic, hepatic, adipocytic, and osteogenic.

2.2 Need for xeno-free culture systems

Conventionally, human embryonic stem cell lines are grown 1) in a medium containing animal serum as a source of nutrients and growth factors and 2) on mouse-derived fibroblast as feeder layers, which play a role in the proliferation and inhibition of their differentiation. However, the use of any cell based therapeutic agent in human must be free of animal contaminations which may contain certain pathogens or xenogens that can trigger immune reactions after transfer to a host. Some laboratories have successfully cultured hESC in a serum-free defined medium on human cell-derived feeders or even in feeder free conditions [18 19]. Another significant achievement in this context was the derivation and establishment of a hESC line under animal product free condition [20].

Expression of a nonhuman sialic acid Neu5Gc and presence of murine viruses are two concerns in existing hESCs grown in presence of animal products or feeders [21]. Replacement of animal serum with human serum has been reported to reduce the expression of Neu5Gc in the hESCs, also Amit et al (2005) have reported the absence of murine leukemia virus in a number of hESC lines maintained on mouse feeders [22]. These studies are largely indicative of the fact that the problem of animal product contamination in the existing culture would be possibly solved in the near future.

2.3 Risk of tumors

Following transplantation hES cell based therapies involves the risk of tumor formation arising from undifferentiated population of the transplanted cells. Studies with both ESCs and ES derived differentiated cells have shown that they can form teratocarcinomas in adult mice if injected subcutaneously, intramuscularly or into the testis [5, 8, 23, 24]. It has also not been possible to produce a pure population of more that 80% of differentiated cells from mouse or human ESCs using any of the directed differentiation protocols. In a cell culture for therapeutic use, the presence of even one undifferentiated cell may potentially lead to teratomas, a cancerous tumor which is derived from germ cells and can from all the three germ layers.

One way of obtaining a pure culture of differentiated cells would be to confirm a negative expression for Oct4 or Nanog in them. Also new strategies can be developed which in some way would tag the ESC implants that could accidentally forms tumors, with death or suicide signals [25]. Alternatively, ESCs can be genetically engineered so that a negative selection can be carried out based on a compound that is toxic to undifferentiated ESCs under certain culture conditions [26]. Studies with mouse ESC show that if a more differentiated cell population is used for grafting, the cells are less likely to generate a tumor [27]. A differentiated population of cells can be segregated from a mixed cell population using either a technique like Fluorescence Activated Cell Sorting (FACS) or other selective approaches [28, 29]. Bieberich et al., (2004) showed that treating the mixed population with the ceramide analogue N-oleoyl serinol (S18) can selectively induce apoptosis of ESCs [30]. While adequate technologies for screening and generating a pure population of differentiated stem cells are available, it is yet not known whether they are capable of eliminating each and every potential tumor forming ES cell.

2.4 Genetic instability

Questions on the suitability of ESCs for transplantation purpose is raised because of the observed genetic instability of cloned cells and extreme inefficiency of the process [31]. Cloned animals like Dolly give the outward appearance of full health, but the probability of their having numerous genetic defects is very high. Hochedlinger and Rudolf Jaenisch (2002) showed that in mice, cloned using ESC in place of the somatic cells (which produces better results) the reprogramming of the inserted genetic material by the embryonic cells proceeded in a very unregulated way [32]. They reported that many of the genes that are necessary for the early phase of embryonic development were not activated.

2.5 Transplant rejection

The immune system tends to reject the transplanted ESCs as 'foreign'. This rejection can be inhibited by the use of immunosuppressive drugs which can have serious side effects. Alternate approaches using homolologous recombination techniques can allow the host immune system to recognize and mark the ESCs as 'self'. This is possible by replacing the MHC genes in ESCs with the host MHC genes [33]. Elimination of MHC class I and II gene loci is also proposed, though this would be technically challenging and would be clinically problematic because cells lacking MHC class I surface expression are targeted by NK cells [34, 35].

One possible alternative is to establish a bank of MHC-compatible hESC lines. Taylor et al., (2005) reported that a reasonable HLA match for around 85% of the UK population could be achieved with around 150 lines [36]. However, this number might be conservative for countries like India and the USA, which have a varied and multi-racial population [37]. Even with such banks in most cases immunosuppressive drugs would still be needed for most donor patient combinations. Some also believe that the transplantation of hESC derivatives into immune-privileged sites such as the brain, say to treat Parkinson's disease, may possibly ameliorate the adverse effects of a MHC-mismatch, although the protection would only be short term.

A possible way to overcome immune rejection is to over express genes that can suppress the immune system such as fas-ligand into ES cells [38]. It is suggested that removal of certain cell surface molecules like B7 antigens or CD40 ligands that are immunologically reactive from ES cells prior to transplantation could suppress immune rejections. For this, somatic cell nucleus from the recipient/patient can be subjected to such genetic modifications and can be inserted into an enucleated oocyte. Though this technology would help in developing patient specific ESCs lines, it would also carry along with it several ethical and technical limitations [32]. As in most incurables diseases, if the patient is suffering from a degenerative condition which destroys their own cells, the transplanted ESCs will suffer the same fate. Therefore in such cases transplanting a population of cells that includes a proliferating progenitor is needed to provide a continuous source of differentiating cells. Again as discussed earlier these transplants might run the risk of tumor formation.

2.6 Epigenetic reprogramming and culture adaptation

HESC lines can differ from each other in their genomic expression profiles through epigenetic regulations. Two major causes for epigenetic changes in hESCs have been identified; 1) the epigenetic changes in preimplantation embryos used for derivation of the hES cell lines, and 2) epigenetic changes during their maintenance in the culture over time.

Epigenetic changes in embryos

In the preimplantation embryos epigenetic modifications such as DNA methylation and histone modifications are widely involved in the regulation of imprinted and non-imprinted genes. These events are often vulnerable to the external environment or culture conditions. Ericson and Kallen, (2001) have reported the occurrences of congenital malformations after the use of assisted reproductive technologies (ART) in human [39]. ART has also been linked to imprinting disorders, such as Beckwith-Wiedemann Syndrome and Angelman Syndrome (AS) [40, 41]. It has been shown that these disorders result from hypomethylation of the maternal genome [42, 43]. A set of a few such methylated and imprinted genes like TSSC5, H19, PEG1, SNRPN, Xist, Oct4, Notch1, DLK1 etc., are now being studied for their methylation status as a part of the characterization process for new hESC lines [44]. More elaborate studies on various existing hESC lines are required to identify the epigenetic markers for pluripotency. Most existing hESC lines have been established under different culture conditions, this might cause variations in epigenetic profiles over and above that inherited from in-vitro production of the embryo [45].

Epigenetic changes over time

Human ESCs can be used as suitable models for genetic defects, diseases, drug screening and cell replacement therapies only if they are genetically stable over long periods in culture. However, a recent report by Allergrucci et al., (2007), shows that hESCs can undergo epigenetic changes over time in culture [46]. They found maximum changes in the epigenetic profile of these cells at the early stages post derivation and after growing them in serum free culture systems [47]. In another report a DNA methylation profile for hESC was determined, and a set of 25 sites from 23 genes were also identified, which could distinguish normal hESCs from differentiated cells [48]. Lagarkowa et al., (2006) demonstrated that the methylation status of pluripotency genes like DPPA3 and DPPA5 varied between hESC lines and also during their differentiation into embryoid bodies [49]. All these studies indicate the need for optimization of procedures that would minimize culture-induced genomic instability. This also implies that periodic monitoring of these lines will be required to evaluate their suitability for in-vivo applications. It is possible that hESCs can get rapidly reprogrammed into unpredictable genetic changes and that some existing and late-passage hESC lines may not be suitable for therapeutic uses.

2.7 Chromosomal abnormalities during prolonged culture

Selection and adaptation of hESCs is a poorly understood phenomenon. An extreme variability in culture conditions exist not only between labs, but even within laboratories. The establishment and maintenance of these cells must involve some form of 'culture adaptation' process, most like epigenetic in nature as discussed above. However, several reports also indicate that these cells acquire chromosomal abnormalities or karyotype aberrations during prolonged culture in parallel with epigenetic changes [50]. Such adaptations may result in enhanced cloning efficiencies after plating single cells [51], a reduced tendency for apoptosis [52], and is expected to have a reduced capacity for differentiation which is difficult to assess quantitatively. A recent report by Baker et al., (2007) demonstrates clear evidence for the accumulation of specific chromosomal aberrations within several well-established hESC lines over time [53]. Results from previously published data were pooled and compared with their own data to access the temporal affects of long term in vitro maintenance on the genetic stability of hESC lines. The study indicates that hESCs indeed become chromosomally abnormal and 'culture adapted' in a reproducible, non-random nature over time. They also found a bias for gains in chromosomes 12, 17, and X, which are similar to chromosomal change seen in breast cancer and testicular germ cell tumor (TGCT) seminomas and non-seminomas. This indicates that these chromosomal regions may harbor replication dependent genes critical for cell proliferation. Interestingly, antiapoptotic genes like BIRC5; pluripotency genes like NANOG, DPPA3, and GDF3; cell-cycle regulator like CCND2; and other genes involved in cancer tumorigenesis like TGCT1, KRAS and SOX5, lie in chromosome 17, chromosome 12, and the X chromosome [53]. With all these evidences it is becoming increasingly clear that standard immuno-markers commonly employed to identify hESCs are not adequate to demonstrate that the hESCs are normal.

3. Embryonic stem cell based therapies: advances

What may have appeared to be impossible with ESC research several years ago is gradually turning into reality. Scientists are trying to coax the ES cells to differentiated population of cells which could be used for therapies. For a list of in vitro differentiated cell types derived from hESCs by various groups please refer to Deb et al., (2007) [54]. A list of preclinical animal models where human ESCs have demonstrated efficiency is listed in Table 1. Besides this scientists are trying to use ESCs for various other applications. For example, the use of ESCs as vehicles for tropic support for dying neurons is possibly a more feasible goal and many workers are focusing on this kind of studies [41]. Efforts are being made to use this technology, to modify the ESCs for use in delivery of genes and other factors to dying motor neurons.

Table 1 A list of animal injury and disease models where hESCs have been shown to be effective

Generation of patient specific human nuclear transfer ESC (hNT-ESCs) lines is a strategy that may circumvent the problem of immuno-rejection which is the greatest challenge in CRTs [55]. The implications of transferring mitochondrial hetroplasmic cells, which might contain aberrant epigenetic gene expression profiles, are also of concern. Allogenic mitochondria present in the NT-ESC derived cells could be recognized by the host immune system, leading to disrupted mitochondrial membrane potential that induces apoptosis [52, 56]. The mitochondrial genome is also known to encode a number of transplantation antigens that could trigger a immune response for the host tissue following engraftment [57], for example the maternally transmitted mtDNA-encoded minor histocompatibility antigen (mi-Has) [58, 59]. This has been demonstrated in failed cardiomyocyte grafts with mitocondria induced apoptosis in a rat model [60].

Pathenogenetically activated embryos has been proposed for the creation of female haploid ESC lines. These cells could serve as an autologous source of cells for producing differentiated cell types to treat women suffering from diseases like Type 1 diabetes or spinal cord injuries [61]. This possibility has been tested in a primate model [62]. However, it is not know if a differentiated haploid cell type following a transplant would remain normal in-vivo. Recently Revazova et al., (2007) has reported the development of six patient specific stem cell lines from parthenogenetic blastocysts [63]. They have also used a protocol which minimizes the use of animal derived components to make the cell lines more suitable for clinical applications.

Despite the drawbacks and debates, an internet search shows some commercial sources offering embryonic stem cell therapy, like the Embryonic Tissues Center, in the Ukraine; Nu Tech Mediworld, in India; and Medra Inc., in the Dominican Republic. However, as there are no peer reviewed publications on Medline from these groups, nothing is known about how they prepare the cells, how the safety and side effects are evaluated, and how credible their claims are. There is a need to increase public awareness and to manage the public expectations for hESC based therapies. The ESC research programs being undertaken by corporations such as Geron Corporation, CA, USA, Advanced Cell Technology, CA, USA pave the way for better planned and transparent procedures employed embryonic stem cell therapy [64, 65]. However, extensive research is still required to streamline hESC differentiation and develop cell transplantation methodologies. The recent reports of reprogrammed adult cells yielding the induced pluripotent cells may put an end to the ethical debates over the use of human oocytes to create stem cells [12, 66]. Also the derivation of embryonic stem cell lines that are "HLA-homozygous," now provides avenues to overcome the problem of immune rejection and may pave way to utilize ESCs as therapeutics [67]. Trivedi et al., (2006) has reported a unique technique for tolerance induction using nuclear transfer (NT)-hESC-induced hematopoietic chimerism with synergistic use of adult bone marrow [68]. This nuclear transfer (NT)-hESC line was derived by transferring a donor cumulus cell into an enucleated oocyte, and subjected to electrical fusion followed by culture for 5 days. Although these reports are very promising a great deal of preclinical research still needs to be undertaken before the envisioned therapeutic potential of ESCs can be translated to the bedside. With more number of countries involving themselves in human ESC research it is expected that the progress will be faster and the technology may be brought to a clinical platform sooner than we may predict.



Human embryonic stem cells


Cell replacement therapies


Inner cell mass


In vitro fertilization


Somatic cell nuclear transfer


Preimplantation genetic diagnosis


Blastomere-like stem cells


Embryonic-like stem cells


Fluorescence Activated Cell Sorting


Assisted reproductive technologies


Human nuclear transfer ESC.


  1. 1.

    Evans MJ, Kaufman MH: Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981, 292: 154-156. 10.1038/292154a0.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Cole RJ, Edwards RG, Paul J: Cytodifferentiation and embryogenesis in cell colonies and tissue cultures derived from ova and blastocysts of the rabbit. Dev Biol. 1966, 13: 385-407. 10.1016/0012-1606(66)90056-X.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM: Embryonic stem cell lines derived from human blastocysts. Science. 1998, 282: 1145-1147. 10.1126/science.282.5391.1145.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Keller G: Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev. 2005, 19: 1129-1155. 10.1101/gad.1303605.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Itskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M, Soreq H, Benvenisty N: Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med. 2000, 6: 88-95.

    PubMed Central  CAS  PubMed  Google Scholar 

  6. 6.

    Gerecht-Nir S, Itskovitz-Eldor J: Cell therapy using human embryonic stem cells. Transpl Immunol. 2004, 12: 203-209. 10.1016/j.trim.2003.12.013.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Raff M: Adult stem cell plasticity: fact or artifact?. Annu Rev Cell Dev Biol. 2003, 19: 1-22. 10.1146/annurev.cellbio.19.111301.143037.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Chung Y, Klimanskaya I, Becker S, Marh J, Lu SJ, Johnson J, Meisner L, Lanza R: Embryonic and extraembryonic stem cell lines derived from single mouse blastomeres. Nature. 2006, 439: 216-219. 10.1038/nature04277.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R: Human embryonic stem cell lines derived from single blastomeres. Nature. 2006, 444: 481-485. 10.1038/nature05142.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Cowan CA, Atienza J, Melton DA, Eggan K: Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science. 2005, 309: 1369-1373. 10.1126/science.1116447.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Hurlbut WB: Altered nuclear transfer as a morally acceptable means for the procurement of human embryonic stem cells. Natl Cathol Bioeth Q. 2005, 5: 145-151.

    Article  PubMed  Google Scholar 

  12. 12.

    Meissner A, Jaenisch R: Generation of nuclear transfer-derived pluripotent ES cells from cloned Cdx2-deficient blastocysts. Nature. 2006, 439: 212-215. 10.1038/nature04257.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R: Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells. Science. 2007, 318: 1917-1920. 10.1126/science.1151526.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Takahashi K, Yamanaka S: Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell. 2007, 126: 663-676. 10.1016/j.cell.2006.07.024.

    Article  Google Scholar 

  15. 15.

    Hanna J, Wernig M, Markoulaki S, Sun C-W, Meissner A, Cassady JP, Beard C, Brambrink T, Wu L-C, Townes TM, Jaenisch R: Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin. Science. 2007, 318 (5858): 1920-3. 10.1126/science.1152092.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Young HE, Duplaa C, Katz R, Thompson T, Hawkins KC, Boev AN, Henson NL, Heaton M, Sood R, Ashley D: Adult-derived stem cells and their potential for use in tissue repair and molecular medicine. Cell Mol Med. 2005, 9 (3): 753-69. 10.1111/j.1582-4934.2005.tb00510.x.

    Article  Google Scholar 

  17. 17.

    Meng X, Ichim TE, Zhong J, Rogers A, Yin Z, Jackson J, Wang H, Ge W, Bogin V, Chan KW, Thebaud B, Riordan NH: Endometrial regenerative cells: A novel stem cell population. J Trans Med. 2007, 5 (1): 57-10.1186/1479-5876-5-57.

    CAS  Article  Google Scholar 

  18. 18.

    Amit M, Shariki C, Margulets V, Itskovitz-Eldor J: Feeder layer- and serum-free culture of human embryonic stem cells. Biol Reprod. 2004, 70: 837-845. 10.1095/biolreprod.103.021147.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Xu C, Inokuma MS, Denham J, Golds K, Kundu P, Gold JD, Carpenter MK: Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotechnol. 2001, 19: 971-974. 10.1038/nbt1001-971.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Ludwig TE, Levenstein ME, Jones JM, Berggren WT, Mitchen ER, Frane JL, Crandall LJ, Daigh CA, Conard KR, Piekarczyk MS: Derivation of human embryonic stem cells in defined conditions. Nat Biotechnol. 2006, 24: 185-187. 10.1038/nbt1177.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Martin MJ, Muotri A, Gage F, Varki A: Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med. 2005, 11: 228-232. 10.1038/nm1181.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Amit M, Winkler ME, Menke S, Bruning E, Buscher K, Denner J, Haverich A, Itskovitz-Eldor J, Martin U: No evidence for infection of human embryonic stem cells by feeder cell-derived murine leukemia viruses. Stem Cells. 2005, 23: 761-771. 10.1634/stemcells.2004-0046.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Odorico JS, Kaufman DS, Thomson JA: Multilineage differentiation from human embryonic stem cell lines. Stem Cells. 2001, 19: 193-204. 10.1634/stemcells.19-3-193.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Wernig M, Benninger F, Schmandt T, Rade M, Tucker KL, Bussow H, Beck H, Brustle O: Functional integration of embryonic stem cell-derived neurons in vivo. J Neurosci. 2004, 24: 5258-5268. 10.1523/JNEUROSCI.0428-04.200.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Doss MX, Koehler CI, Gissel C, Hescheler J, Sachinidis A: Embryonic stem cells: a promising tool for cell replacement therapy. J Cell Mol Med. 2004, 8: 465-473. 10.1111/j.1582-4934.2004.tb00471.x.

    Article  PubMed  Google Scholar 

  26. 26.

    Billon N, Jolicoeur C, Ying QL, Smith A, Raff M: Normal timing of oligodendrocyte development from genetically engineered, lineage-selectable mouse ES cells. J Cell Sci. 2002, 115: 3657-3665. 10.1242/jcs.00049.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Dani C, Smith AG, Dessolin S, Leroy P, Staccini L, Villageois P, Darimont C, Ailhaud G: Differentiation of embryonic stem cells into adipocytes in vitro. J Cell Sci. 1997, 110 (Pt 11): 1279-1285.

    CAS  PubMed  Google Scholar 

  28. 28.

    Aubert J, Stavridis MP, Tweedie S, O'Reilly M, Vierlinger K, Li M, Ghazal P, Pratt T, Mason JO, Roy D, Smith A: Screening for mammalian neural genes via fluorescence-activated cell sorter purification of neural precursors from Sox1-gfp knock-in mice. Proc Natl Acad Sci U S A. 2003, 100 (Suppl 1): 11836-11841. 10.1073/pnas.1734197100.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  29. 29.

    Klug MG, Soonpaa MH, Koh GY, Field LJ: Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafts. J Clin Invest. 1996, 98: 216-224. 10.1172/JCI118769.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  30. 30.

    Bieberich E, Silva J, Wang G, Krishnamurthy K, Condie BG: Selective apoptosis of pluripotent mouse and human stem cells by novel ceramide analogues prevents teratoma formation and enriches for neural precursors in ES cell-derived neural transplants. J Cell Biol. 2004, 167: 723-734. 10.1083/jcb.200405144.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  31. 31.

    Sung LY, Gao S, Shen H, Yu H, Song Y, Smith SL, Chang CC, Inoue K, Kuo L, Lian J: Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer. Nat Genet. 2006, 38: 1323-1328. 10.1038/ng1895.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Hochedlinger K, Jaenisch R: Nuclear transplantation: lessons from frogs and mice. Curr Opin Cell Biol. 2002, 14: 741-748. 10.1016/S0955-0674(02)00380-0.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Hardy RR, Malissen B: Lymphocyte development. The (knock-) ins and outs of lymphoid development. Curr Opin Immunol. 1998, 10: 155-157. 10.1016/S0952-7915(98)80243-4.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Makrigiannis AP, Anderson SK: Regulation of natural killer cell function. Cancer Biol Ther. 2003, 2: 610-616.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Rideout WM, Hochedlinger K, Kyba M, Daley GQ, Jaenisch R: Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell. 2002, 109: 17-27. 10.1016/S0092-8674(02)00681-5.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Taylor CJ, Bolton EM, Pocock S, Sharples LD, Pedersen RA, Bradley JA: Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet. 2005, 366: 2019-2025. 10.1016/S0140-6736(05)67813-0.

    Article  PubMed  Google Scholar 

  37. 37.

    Rao MS, Auerbach JM: Estimating human embryonic stem-cell numbers. Lancet. 2006, 367: 650-10.1016/S0140-6736(06)68261-5.

    Article  PubMed  Google Scholar 

  38. 38.

    Martinez OM, Krams SM: Involvement of Fas-Fas ligand interactions in graft rejection. Int Rev Immunol. 1999, 18: 527-546.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Ericson A, Kallen B: Congenital malformations in infants born after IVF: a population-based study. Hum Reprod. 2001, 16: 504-509. 10.1093/humrep/16.3.504.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    DeBaun MR, Niemitz EL, Feinberg AP: Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet. 2003, 72: 156-160. 10.1086/346031.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  41. 41.

    Hamada M, Yoshikawa H, Ueda Y, Kurokawa MS, Watanabe K, Sakakibara M, Tadokoro M, Akashi K, Aoki H, Suzuki N: Introduction of the MASH1 gene into mouse embryonic stem cells leads to differentiation of motoneuron precursors lacking Nogo receptor expression that can be applicable for transplantation to spinal cord injury. Neurobiol Dis. 2006, 22: 509-522. 10.1016/j.nbd.2005.12.020.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Halliday J, Oke K, Breheny S, Algar E, D JA: Beckwith-Wiedemann syndrome and IVF: a case-control study. Am J Hum Genet. 2004, 75: 526-528. 10.1086/423902.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  43. 43.

    Cox GF, Burger J, Lip V, Mau UA, Sperling K, Wu BL, Horsthemke B: Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am J Hum Genet. 2002, 71: 162-164. 10.1086/341096.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  44. 44.

    Plaia TW, Josephson R, Liu Y, Zeng X, Ording C, Toumadje A, Brimble SN, Sherrer ES, Uhl EW, Freed WJ: Characterization of a new NIH-registered variant human embryonic stem cell line, BG01V: a tool for human embryonic stem cell research. Stem Cells. 2006, 24: 531-546. 10.1634/stemcells.2005-0315.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Wrenzycki C, Niemann H: Epigenetic reprogramming in early embryonic development: effects of in-vitro production and somatic nuclear transfer. Reprod Biomed Online. 2003, 7: 649-656.

    Article  PubMed  Google Scholar 

  46. 46.

    Allegrucci C, Wu YZ, Thurston A, Denning CN, Priddle H, Mummery CL, Ward-van Oostwaard D, Andrews PW, Stojkovic M, Smith N: Restriction landmark genome scanning identifies culture-induced DNA methylation instability in the human embryonic stem cell epigenome. Hum Mol Genet. 2007, 16: 1253-1268. 10.1093/hmg/ddm074.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Maitra A, Arking DE, Shivapurkar N, Ikeda M, Stastny V, Kassauei K, Sui G, Cutler DJ, Liu Y, Brimble SN: Genomic alterations in cultured human embryonic stem cells. Nat Genet. 2005, 37: 1099-1103. 10.1038/ng1631.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Bibikova M, Chudin E, Wu B, Zhou L, Garcia EW, Liu Y, Shin S, Plaia TW, Auerbach JM, Arking DE: Human embryonic stem cells have a unique epigenetic signature. Genome Res. 2006, 16: 1075-1083. 10.1101/gr.5319906.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  49. 49.

    Lagarkova MA, Volchkov PY, Lyakisheva AV, Philonenko ES, Kiselev SL: Diverse epigenetic profile of novel human embryonic stem cell lines. Cell Cycle. 2006, 5: 416-420.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Mitalipova MM, Rao RR, Hoyer DM, Johnson JA, Meisner LF, Jones KL, Dalton S, Stice SL: Preserving the genetic integrity of human embryonic stem cells. Nat Biotechnol. 2005, 23: 19-20. 10.1038/nbt0105-19.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Enver T, Soneji S, Joshi C, Brown J, Iborra F, Orntoft T, Thykjaer T, Maltby E, Smith K, Dawud RA: Cellular differentiation hierarchies in normal and culture-adapted human embryonic stem cells. Hum Mol Genet. 2005, 14: 3129-3140. 10.1093/hmg/ddi345.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Kristal BS, Stavrovskaya IG, Narayanan MV, Krasnikov BF, Brown AM, Beal MF, Friedlander RM: The mitochondrial permeability transition as a target for neuroprotection. J Bioenerg Biomembr. 2004, 36: 309-312. 10.1023/B:JOBB.0000041759.35731.70.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Baker DE, Harrison NJ, Maltby E, Smith K, Moore HD, Shaw PJ, Heath PR, Holden H, Andrews PW: Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat Biotechnol. 2007, 25: 207-215. 10.1038/nbt1285.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Sivasubramaniyan K, Atluri RR, Sarda K, Arvind M, Balaji V, Deb KD: Endotoxin-induced silencing of mesoderm induction and functional differentiation: role of HMGB1 in pluripotency and infection. Regen Med. 2008, 3 (1): 23-31. 10.2217/17460751.3.1.23.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Hall VJ, Stojkovic P, Stojkovic M: Using therapeutic cloning to fight human disease: a conundrum or reality?. Stem Cells. 2006, 24: 1628-1637. 10.1634/stemcells.2005-0592.

    Article  PubMed  Google Scholar 

  56. 56.

    Lanza RP, Chung HY, Yoo JJ, Wettstein PJ, Blackwell C, Borson N, Hofmeister E, Schuch G, Soker S, Moraes CT: Generation of histocompatible tissues using nuclear transplantation. Nat Biotechnol. 2002, 20: 689-696. 10.1038/nbt703.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Zavazava N, Kabelitz D: Alloreactivity and apoptosis in graft rejection and transplantation tolerance. J Leukoc Biol. 2000, 68: 167-174.

    CAS  PubMed  Google Scholar 

  58. 58.

    Dabhi VM, Lindahl KF: MtDNA-encoded histocompatibility antigens. Methods Enzymol. 1995, 260: 466-485.

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Fischer Lindahl K, Hermel E, Loveland BE, Wang CR: Maternally transmitted antigen of mice: a model transplantation antigen. Annu Rev Immunol. 1991, 9: 351-372. 10.1146/annurev.iy.09.040191.002031.

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    Raisky O, Gomez L, Chalabreysse L, Gateau-Roesch O, Loufouat J, Thivolet-Bejui F, Ninet J, Ovize M: Mitochondrial permeability transition in cardiomyocyte apoptosis during acute graft rejection. Am J Transplant. 2004, 4: 1071-1078. 10.1111/j.1600-6143.2004.00473.x.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Kiessling AA: Eggs alone. Nature. 2005, 434: 145-10.1038/434145a.

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Vrana KE, Hipp JD, Goss AM, McCool BA, Riddle DR, Walker SJ, Wettstein PJ, Studer LP, Tabar V, Cunniff K: Nonhuman primate parthenogenetic stem cells. Proc Natl Acad Sci U S A. 2003, 100 (Suppl 1): 11911-11916. 10.1073/pnas.2034195100.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  63. 63.

    Revazova ES, Turovets NA, Kochetkova OD, Kindarova LB, Kuzmichev LN, Janus JD, Pryzhkova MV: Patient-specific stem cell lines derived from human parthenogenetic blastocysts. Cloning Stem Cells. 2007, 9: 432-449. 10.1089/clo.2007.0033.

    CAS  Article  PubMed  Google Scholar 

  64. 64.

    Lund RD, Wang S, Klimanskaya I, Holmes T, Ramos-Kelsey R, Lu B, Girman S, Bischoff N, Sauve Y, Lanza R: Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning Stem Cells. 2006, 8: 189-199. 10.1089/clo.2006.8.189.

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    Lebkowski JS, Gold J, Xu C, Funk W, Chiu C-K, Carpenter MK: Human embryonic stem cells: culture differentiation and genetic modification for regenerative medicine applications. The Cancer Journal. 2001, 7 (2): 83-93.

    Google Scholar 

  66. 66.

    Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM: Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin. Science. 2007, 318: 1920-1923. 10.1126/science.1152092.

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    Revazova ES, Turovets NA, Kochetkova OD, Agapova S, Sebastian JL, Pryzhkova MV, Smolinkova VIU, Kuzmichev LN: HLA Homozygous Stem Cell Lines Derived from Human Parthenogenetic Blastocysts. Cloning Stem Cells. 2008, 10 (1): 11-24. 10.1089/clo.2007.0063.

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    Trivedi HL, Mishra VV, Vanikar AV, Modi PR, Shah VR, Shah PR, Firoz A: Embryonic stem cell derived and adult hematopoietic stem cell transplantation for tolerance induction in a renal allograft recipient: – a case report. Transplant Proc. 2006, 38 (9): 3103-8. 10.1016/j.transproceed.2006.08.173.

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Keirsted HS, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K, Steward O: Human Embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci. 2005, 25 (19): 4694-705. 10.1523/JNEUROSCI.0311-05.2005.

    Article  Google Scholar 

  70. 70.

    Nakamura M, Okano H, Toyama Y, Dai HN, Finn TP, Bergman BS: Transplantation of embryonic spinal cord-derived neurospheres support growth of supraspinal projections and functional recovery after spinal cord injury in the neonatal rat. J Neurosci Res. 2005, 81 (4): 457-468. 10.1002/jnr.20580.

    CAS  Article  PubMed  Google Scholar 

  71. 71.

    Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, Reinecke H, Xu C, Hassanipour M, Police S: Cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol. 2007, 25 (9): 1015-24. 10.1038/nbt1327.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Leor J, Patterson M, Quinones MJ, Kedes LH, Kloner RA: Transplantation of fetal myocardial tissue into the infracted myocardium of rat. A potential method for repair of infracted myocardium?. Circulation. 1996, 94 (Suppl 9): II332-II336.

    CAS  PubMed  Google Scholar 

  73. 73.

    Kehat I, Khimovich L, Capsi O, Gepstein A, Shofti R, Arbel G, Huber I, Satin J, Itskovitz-Eldor J, Gepstein L: Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol. 2004, 22: 1282-1289. 10.1038/nbt1014.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Caspi O, Huber I, Kehat I, Habib M, Arbel G, Gepstein A, Yankelson L, Aronson D, Beyar R, Gepstein L: Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol. 2007, 50 (19): 1884-93. 10.1016/j.jacc.2007.07.054.

    Article  PubMed  Google Scholar 

  75. 75.

    Seo MJ, Suh SY, Bae YC, Jung JS: Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun. 2005, 328 (1): 258-264. 10.1016/j.bbrc.2004.12.158.

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Muschler GF, Nitto H, MAtsukura Y, Boehm C, Valdevit A, Kambic H, Davros W, Powell K, Easley K: Spine fusion using cell matrix composites enriched in bone marrow-derived cells. Clin Orthop. 2003, 407: 102-118. 10.1097/00003086-200302000-00018.

    Article  PubMed  Google Scholar 

  77. 77.

    Cho SW, Gwak SJ, Kang SW, Bhang SH, Won Song KW, Yang YS, Choi CY, Kim BS: Enhancement of angiogenic efficacy of human cord blood cell transplantation. Tissue Eng. 2006, 12 (6): 1651-61. 10.1089/ten.2006.12.1651.

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Song J, Lee ST, Kang W, Park JE, Chu K, Lee SE, Hwang T, Chung H, Kim M: Human embryonic stem cell-derived neural precursor transplants attenuate apomorphine-induced rotational behavior in rats with unilateral quinolinic acid lesions. Neurosci Lett. 2007, 423 (1): 58-61. 10.1016/j.neulet.2007.05.066.

    CAS  Article  PubMed  Google Scholar 

  79. 79.

    Shim JH, Kim SE, Woo DH, Kim SK, Oh CH, McKay R, Kim JH: Directed differentiation of human embryonic stem cells towards a pancreatic cell fate. Diabetologia. 2007, 50 (6): 1228-38. 10.1007/s00125-007-0634-z.

    CAS  Article  PubMed  Google Scholar 

  80. 80.

    Barberi T, Bradbury M, Dincer Z, Panagiotakos G, Socci ND, Studer L: Derivation of engraftable skeletal myoblasts from human embryonic stem cells. Nat Med. 2007, 13 (5): 642-8. 10.1038/nm1533.

    CAS  Article  PubMed  Google Scholar 

  81. 81.

    Sonntag KC, Pruszak J, Yoshizaki T, van Arensbergen J, Sanchez-Pernaute R, Isacson O: Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist noggin. Stem Cells. 2007, 25 (2): 411-8. 10.1634/stemcells.2006-0380.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  82. 82.

    Ben-Hur T, Idelson M, Khaner H, Pera M, Reinhartz E, Itzik A, Reubinoff BE: Transplantation of human embryonic stem cell-derived neural progenitors improves behavioral deficit in Parkinsonian rats. Stem Cells. 2004, 22 (7): 1246-55. 10.1634/stemcells.2004-0094.

    Article  PubMed  Google Scholar 

  83. 83.

    Lee DH, Kim EY, Park S, Phi JH, Kim SK, Cho BK, Lim J, Wang KC: Reclosure of surgically induced spinal open neural tube defects by the intraamniotic injection of human embryonic stem cells in chick embryos 24 hours after lesion induction. J Neurosurg. 2006, 105 (2 Suppl): 127-33.

    PubMed  Google Scholar 

  84. 84.

    Galic Z, Kitchen SG, Kacena A, Subramanian A, Burke B, Cortado R, Zack JA: T lineage differentiation from human embryonic stem cells. Proc Natl Acad Sci. 2006, 103 (31): 11742-7. 10.1073/pnas.0604244103.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

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We are thankful to Stempeutics Research Pvt. Ltd. for internal funding. We are also thankful to Dr. Satish Totey for revising the manuscript.

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Correspondence to Kaushik Dilip Deb.

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The author(s) declare that they have no competing interests.

Authors' contributions

KD has written the initial manuscript and compiled the information. KS has added the references and recent updates in the area. Both KD and KS have revised and read the manuscript before final approval. All authors have read and approved the final manuscript.

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Deb, K.D., Sarda, K. Human embryonic stem cells: preclinical perspectives. J Transl Med 6, 7 (2008).

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