Skip to main content
NCBI home page
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;8(4):465–473. doi: 10.1111/j.1582-4934.2004.tb00471.x

Embryonic stem cells: a promising tool for cell replacement therapy

Michael Xavier Doss 1, Christoph I Koehler 1, C Gissel 1, Jürgen Hescheler 1, Agapios Sachinidis 1,✉
PMCID: PMC6740107  PMID: 15601575

Abstract

Embryonic stem (ES) cells are revolutionizing the field of developmental biology as a potential tool to understand the molecular mechanisms occurring during the process of differentiation from the embryonic stage to the adult phenotype. ES cells harvested from the inner cell mass (ICM) of the early embryo can proliferate indefinitely in vitro while retaining the ability to differentiate into all somatic cells. Emerging results from mice models with ES cells are promising and raising tremendous hope among the scientific community for the ES‐cell based cell replacement therapy (CRT) of various severe diseases. ES cells could potentially revolutionize medicine by providing an unlimited renewable source of cells capable of replacing or repairing tissues that have been damaged in almost all degenerative diseases such as diabetes, myocardial infarction and Parkinson's disease. This review updates the progress of ES cell research in CRT, discusses about the problems encountered in the practical utility of ES cells in CRT and evaluates how far this approach is successful experimentally.

Keywords: embryonic stem cells, cell replacement therapy

References

  • 1. Asahara T., Kalka C., Isner J.M., Stem cell therapy and gene transfer for regeneration, Gene Ther., 7: 451–457, 2000. [DOI] [PubMed] [Google Scholar]
  • 2. Fodor W. L., Tissue engineering and cell based therapies, from the bench to the clinic: the potential to replace, repair and regenerate, Reprod. Biol. Endocrinol. 1: 102, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Delcarpio J.B., Claycomb W.C., Cardiomyocyte transfer into the mammalian heart. Cell‐to‐cell interactions in vivo and in vitro , Ann. N. Y. Acad. Sci. 752: 267–285, 1995. [DOI] [PubMed] [Google Scholar]
  • 4. Koh G.Y., Soonpaa M.H., Klug M.G., Field L.J., Longterm survival of AT‐1 cardiomyocyte grafts in syngeneic myocardium, Am. J. Physiol. 264: H1727–H1733, 1993. [DOI] [PubMed] [Google Scholar]
  • 5. Koh G.Y., Soonpaa M.H., Klug M.G., Pride H.P., Cooper B.J., Zipes D.P., Field L.J., Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs, J. Clin. Invest. 96: 2034–2042, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Roell W., Lu Z.J., Bloch W., Siedner S., Tiemann K., Xia Y., Stoecker E., Fleischmann M., Bohlen H., Stehle R., Kolossov E., Brem G., Addicks K., Pfitzer G., Welz A., Hescheler J., Fleischmann B.K., Cellular cardiomyoplasty improves survival after myocardial injury, Circulation 105: 2435–2441, 2002. [DOI] [PubMed] [Google Scholar]
  • 7. Evans M.J., Potential for genetic manipulation of mammals, Mol. Biol. Med. 6: 557–565, 1989. [PubMed] [Google Scholar]
  • 8. Martin G.R., Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells, Proc. Natl. Acad. Sci. USA 78: 7634–7638, 1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Williams R.L., Hilton D.J., Pease S., Willson T.A., Stewart C.L., Gearing D.P., Wagner E.F., Metcalf D., Nicola N.A., Gough N.M., Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells, Nature 336: 684–687, 1988. [DOI] [PubMed] [Google Scholar]
  • 10. Graves K.H., Moreadith R.W., Derivation and characterization of putative pluripotential embryonic stem cells from preimplantation rabbit embryos, Mol. Reprod. Dev. 36: 424–433, 1993. [DOI] [PubMed] [Google Scholar]
  • 11. Li M., Zhang D., Hou Y., Jiao L., Zheng X., Wang W.H., Isolation and culture of embryonic stem cells from porcine blastocysts, Mol. Reprod. Dev. 65: 429–434, 2003. [DOI] [PubMed] [Google Scholar]
  • 12. Thomson J.A., Kalishman J., Golos T.G., Durning M., Harris C.P., Becker R.A., Hearn J.P., Isolation of a primate embryonic stem cell line, Proc. Natl. Acad. Sci. USA 92: 7844–7848, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Thomson J.A., Itskovitz‐Eldor J., Shapiro S.S., Waknitz M.A., Swiergiel J.J., Marshall V.S., Jones J.M., Embryonic stem cell lines derived from human blastocysts, Science 282: 1145–1147, 1998. [DOI] [PubMed] [Google Scholar]
  • 14. Sachinidis A., Fleischmann B.K., Kolossov E., Wartenberg M., Sauer H., Hescheler J., Cardiac specific differentiation of mouse embryonic stem cells, Cardiovasc. Res. 58: 278–291, 2003. [DOI] [PubMed] [Google Scholar]
  • 15. 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. 6: 88–95, 2000. [PMC free article] [PubMed] [Google Scholar]
  • 16. Odorico J.S., Kaufman D.S., Thomson J.A., Multilineage differentiation from human embryonic stem cell lines, Stem Cells 19: 193–204, 2001. [DOI] [PubMed] [Google Scholar]
  • 17. Wobus A.M., Grosse R., Schoneich J., Specific effects of nerve growth factor on the differentiation pattern of mouse embryonic stem cells in vitro , Biomed. Biochim. Acta 47: 965–973, 1988. [PubMed] [Google Scholar]
  • 18. Rathjen P.D., Lake J., Whyatt L.M., Bettess M.D., Rathjen J., Properties and uses of embryonic stem cells: prospects for application to human biology and gene therapy, Reprod. Fertil. Dev. 10: 31–47, 1998. [DOI] [PubMed] [Google Scholar]
  • 19. Doetschman T.C., Eistetter H., Katz M., Schmidt W., Kemler R., The in vitro development of blastocystderived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium, J. Embryol. Exp. Morphol. 87: 27–45, 1985. [PubMed] [Google Scholar]
  • 20. Baker R.K., Lyons G.E., Embryonic stem cells and in vitro muscle development, Curr. Top. Dev. Biol. 33: 263–279, 1996. [DOI] [PubMed] [Google Scholar]
  • 21. Keller G., Kennedy M., Papayannopoulou T., Wiles M.V., Hematopoietic commitment during embryonic stem cell differentiation in culture, Mol. Cell Biol. 13: 473–486, 1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Rohwedel J., Maltsev V., Bober E., Arnold H.H., Hescheler J., Wobus A.M., Muscle cell differentiation of embryonic stem cells reflects myogenesis in vivo: developmentally regulated expression of myogenic determination genes and functional expression of ionic currents, Dev. Biol. 164: 87–101, 1994. [DOI] [PubMed] [Google Scholar]
  • 23. Dani C., Smith A.G., Dessolin S., Leroy P., Staccini L., Villageois P., Darimont C., Ailhaud G., Differentiation of embryonic stem cells into adipocytes in vitro , J. Cell Sci. 110: 1279–1285, 1997. [DOI] [PubMed] [Google Scholar]
  • 24. Poliard A., Nifuji A., Lamblin D., Plee E., Forest C., Kellermann O., Controlled conversion of an immortalized mesodermal progenitor cell towards osteogenic, chondrogenic, or adipogenic pathways, J. Cell Biol. 130: 1461–1472, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Risau W., Sariola H., Zerwes H.G., Sasse J., Ekblom P., Kemler R., Doetschman T., Vasculogenesis and angiogenesis in embryonic‐stem‐cell‐derived embryoid bodies, Development 102: 471–478, 1988. [DOI] [PubMed] [Google Scholar]
  • 26. Yamane T., Hayashi S., Mizoguchi M., Yamazaki H., Kunisada T., Derivation of melanocytes from embryonic stem cells in culture, Dev. Dyn. 216: 450–458, 1999. [DOI] [PubMed] [Google Scholar]
  • 27. Brustle O., Jones K.N., Learish R.D., Karram K., Choudhary K., Wiestler O.D., Duncan I.D., McKay R.D., Embryonic stem cell‐derived glial precursors: a source of myelinating transplants, Science 285: 754–756, 1999. [DOI] [PubMed] [Google Scholar]
  • 28. Sachinidis A., Gissel C., Nierhoff D., Hippler‐Altenburg R., Sauer H., Wartenberg M., Hescheler J., Identification of plateled‐derived growth factor‐BB as cardiogenesis‐inducing factor in mouse embryonic stem cells under serum‐free conditions, Cell Physiol Biochem. 13: 423–429, 2003. [DOI] [PubMed] [Google Scholar]
  • 29. Levinson‐Dushnik M., Benvenisty N., Involvement of hepatocyte nuclear factor 3 in endoderm differentiation of embryonic stem cells, Mol. Cell Biol. 17: 3817–3822, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Grepin C., Nemer G., Nemer M., Enhanced cardiogenesis in embryonic stem cells overexpressing the GATA‐4 transcription factor, Development 124: 2387–2395, 1997. [DOI] [PubMed] [Google Scholar]
  • 31. Fujikura J., Yamato E., Yonemura S., Hosoda K., Masui S., Nakao K., Miyazaki J.J., Niwa H., Differentiation of embryonic stem cells is induced by GATA factors, Genes Dev. 16: 784–789, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Kanda S., Shiroi A., Ouji Y., Birumachi J., Ueda S., Fukui H., Tatsumi K., Ishizaka S., Takahashi Y., Yoshikawa M., In vitro differentiation of hepatocyte‐like cells from embryonic stem cells promoted by gene transfer of hepatocyte nuclear factor 3 beta, Hepatol. Res. 26: 225–231, 2003. [DOI] [PubMed] [Google Scholar]
  • 33. Takahashi T., Lord B., Schulze P.C., Fryer R.M., Sarang S.S., Gullans S.R., Lee R.T., Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes, Circulation 107: 1912–1916, 2003. [DOI] [PubMed] [Google Scholar]
  • 34. Ventura C., Maioli M., Asara Y., Santoni D., Scarlata I., Cantoni S., Perbellini A., Butyric and retinoic mixed ester of hyaluronan. A novel differentiating glycoconjugate affording a high throughput of cardiogenesis in embryonic stem cells, J. Biol. Chem. 279: 23574–23579, 2004. [DOI] [PubMed] [Google Scholar]
  • 35. Hardy R.R., Malissen B., Lymphocyte development. The (knock‐) ins and outs of lymphoid development, Curr. Opin. Immunol. 10: 155–157, 1998. [DOI] [PubMed] [Google Scholar]
  • 36. Westphal C.H., Leder P., Transposon‐generated ‘knock‐out’ and ‘knock‐in’ gene‐targeting constructs for use in mice, Curr. Biol. 7: 530–533, 1997. [DOI] [PubMed] [Google Scholar]
  • 37. Harlan D.M., Kirk A.D., The future of organ and tissue transplantation: can T‐cell costimulatory pathway modifiers revolutionize the prevention of graft rejection?, JAMA 282: 1076–1082, 1999. [DOI] [PubMed] [Google Scholar]
  • 38. Walker P.R., Saas P., Dietrich P.Y., Role of Fas ligand (CD95L) in immune escape: the tumor cell strikes back, J. Immunol. 158: 4521–4524, 1997. [PubMed] [Google Scholar]
  • 39. Hochedlinger K., Jaenisch R., Nuclear transplantation, embryonic stem cells, and the potential for cell therapy, N. Engl. J. Med. 349: 275–286, 2003. [DOI] [PubMed] [Google Scholar]
  • 40. Hochedlinger K., Rideout W.M., Kyba M., Daley G.Q., Blelloch R., Jaenisch R., Nuclear transplantation, embryonic stem cells and the potential for cell therapy, Hematol. J. 5 Suppl 3: S114–S117, 2004. [DOI] [PubMed] [Google Scholar]
  • 41. Lovell M.J., Mathur A., The role of stem cells for treatment of cardiovascular disease, Cell Prolif. 37: 67–87, 2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Schuldiner M., Yanuka O., Itskovitz‐Eldor J., Melton D.A., Benvenisty N., Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells, Proc. Natl. Acad. Sci. U. S. A 97: 11307–11312, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Xu C., Police S., Rao N., Carpenter M.K., Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells, Circ. Res. 91: 501–508, 2002. [DOI] [PubMed] [Google Scholar]
  • 44. Kennedy M., Firpo M., Choi K., Wall C., Robertson S., Kabrun N., Keller G., A common precursor for primitive erythropoiesis and definitive haematopoiesis, Nature 386: 488–493, 1997. [DOI] [PubMed] [Google Scholar]
  • 45. Rippon H.J., Bishop A.E., Embryonic stem cells, Cell Prolif. 37: 23–34, 2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Barberi T., Klivenyi P., Calingasan N.Y., Lee H., Kawamata H., Loonam K., Perrier A.L., Bruses J., Rubio M.E., Topf N., Tabar V., Harrison N.L., Beal M.F., Moore M.A., Studer L., Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice, Nat. Biotechnol. 21: 1200–1207, 2003. [DOI] [PubMed] [Google Scholar]
  • 47. Chiba S., Iwasaki Y., Sekino H., Suzuki N., Transplantation of motoneuron‐enriched neural cells derived from mouse embryonic stem cells improves motor function of hemiplegic mice, Cell Transplant. 12: 457–468, 2003. [DOI] [PubMed] [Google Scholar]
  • 48. Bonner‐Weir S., Stem cells in diabetes: what has been achieved, Horm. Res. 60 Suppl 3: 10, 2003. [DOI] [PubMed] [Google Scholar]
  • 49. Soria B., Skoudy A., Martin F., From stem cells to beta cells: new strategies in cell therapy of diabetes mellitus, Diabetologia 44: 407–415, 2001. [DOI] [PubMed] [Google Scholar]
  • 50. Jones E.A., Tosh D., Wilson D.I., Lindsay S., Forrester L.M., Hepatic differentiation of murine embryonic stem cells, Exp. Cell Res. 272: 15–22, 2002. [DOI] [PubMed] [Google Scholar]
  • 51. Rambhatla L., Chiu C.P., Kundu P., Peng Y., Carpenter M.K., Generation of hepatocyte‐like cells from human embryonic stem cells, Cell Transplant. 12: 1–11, 2003. [DOI] [PubMed] [Google Scholar]
  • 52. Hamazaki T., Iiboshi Y., Oka M., Papst P.J., Meacham A.M., Zon L.I., Terada N., Hepatic maturation in differentiating embryonic stem cells in vitro , FEBS Lett. 497: 15–19, 2001. [DOI] [PubMed] [Google Scholar]
  • 53. Yamamoto H., Quinn G., Asari A., Yamanokuchi H., Teratani T., Terada M., Ochiya T., Differentiation of embryonic stem cells into hepatocytes: biological functions and therapeutic application, Hepatology 37: 983–993, 2003. [DOI] [PubMed] [Google Scholar]
  • 54. Yamada T., Yoshikawa M., Kanda S., Kato Y., Nakajima Y., Ishizaka S., Tsunoda Y., In vitro differentiation of embryonic stem cells into hepatocyte‐like cells identified by cellular uptake of indocyanine green, Stem Cells 20: 146–154, 2002. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES