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Transplantation of Embryonic Stem Cells for Myocardial Regeneration and Angiogenesis

  • Yong-Fu Xiao
  • Jiang-Yong Min
  • James P. Morgan
Part of the Contemporary Cardiology book series (CONCARD)

Abstract

Congestive heart failure remains the leading cause of death in developed countries. Myocardial infarction (MI) results in the loss of heart muscle cells, which is the main contributor to the development of heart failure. Classical medical therapy and mechanical left-ventricular assist devices are available for physicians to improve the prognosis of patients with MI and heart failure, but only half of the patients with end-stage heart failure survive the following year (1). At the present time, allogeneic heart transplantation to extend life span and to improve the quality of daily life is probably the preferred alternative treatment for patients with end-stage heart failure, but extreme organ shortage and chronic cardiac rejection limit the therapy. In recent years, research on stem cells is leading scientists to investigate the possibility of cell-based therapies for cardiac repair, often referred to as regenerative or reparative medicine. Stem cell-based cellular cardiomyoplasty (CCM) for cardiomyocyte replacement/regeneration has been evaluated in animal settings (2, 3, 4, 5, 6) and clinical trials (7, 8, 9). Transplantation of exogenous stem cells could regenerate damaged myocardium and improve cardiac function in failing hearts. Such efforts may offer exciting novel options for treating patients with end-stage heart failure.

Keywords

Stem Cell Embryonic Stem Cell Leukemia Inhibitory Factor Human Embryonic Stem Cell Mouse Embryonic Stem Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Kessler PD, Byrne BJ. Myoblast cell grafting into heart muscle: cellular biology and potential applications. Annu Rev Physiol 1999;61:219–242.PubMedCrossRefGoogle Scholar
  2. 2.
    Soonpaa MH, Koh GY, Klug MG, et al. Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium. Science 1994;264:98–101.PubMedCrossRefGoogle Scholar
  3. 3.
    Chiu RCJ, Zibaitis A, Kao RL. Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg 1995;60:12–18.PubMedGoogle Scholar
  4. 4.
    Li RK, Jia ZQ, Weisel RD, et al. Cardiomyocyte transplantation improves heart function. Ann Thorac Surg 1996;62:654–661.PubMedCrossRefGoogle Scholar
  5. 5.
    Leor J, Patterson M, Quinones MJ, et al. Transplantation of fetal myocardial tissue into the infarcted myocardium of rat: a potential method for repair of infarcted myocardium. Circulation 1996;94(Suppl II):II332–II336.PubMedGoogle Scholar
  6. 6.
    Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410:701–706.PubMedCrossRefGoogle Scholar
  7. 7.
    Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002;106(15):1913–1918.PubMedCrossRefGoogle Scholar
  8. 8.
    Tse HF, Kwong YL, Chan JK, et al. Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 2003;361(9351):47–49.PubMedCrossRefGoogle Scholar
  9. 9.
    Perin EC, Dohmann HF, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 2003;107(18):2294–2302.PubMedCrossRefGoogle Scholar
  10. 10.
    Koh GY, Soonpaa MH, Klug MG, et al. Long-term survival of AT-1 cardiomyocyte grafts in syngeneic myocardium. Am J Physiol 1993;264(5 Pt 2):H1727–H1733.PubMedGoogle Scholar
  11. 11.
    Tomita S, Li RK, Weisel RD, et al. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 1999;100(Suppl II):II247–II256.PubMedGoogle Scholar
  12. 12.
    Chedrawy EG, Wang JS, Nguyen DM, et al. Incorporation and integration of implanted myogenic and stem cells into native myocardial fibers: anatomic basis for functional improvements. J Thorac Cardiovasc Surg 2002;124(3):584–590.PubMedCrossRefGoogle Scholar
  13. 13.
    Min JY, Sullivan MF, Yang Y, et al. Significant improvement of heart function by co-transplantation of human mesenchymal stem cells and fetal cardiomyocytes in postinfarcted pigs. Ann Thorac Surg 2002;74(5):1568–1575.PubMedCrossRefGoogle Scholar
  14. 14.
    Min JY, Yang Y, Converso KL, et al. Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats. J Appl Physiol 2002;92:288–296.PubMedCrossRefGoogle Scholar
  15. 15.
    Naito H, Taniguchi S, Kawata T. Embryonic stem cell-derived cardiomyocyte transplantation into the infarcted myocardium. Heart Surg Forum 2002;6(1):1.Google Scholar
  16. 16.
    Min JY, Yang Y, Sullivan MF, et al. Long-term improvement of cardiac function in rats after infarction by transplantation of embryonic stem cells. J Thorac Cardiovasc Surg 2003;25(2):361–369.CrossRefGoogle Scholar
  17. 17.
    Yang Y, Min JY, Rana JS, et al. VEGF enhances functional improvement of postinfarcted hearts by transplantation of ESC-differentiated cells. J Appl Physiol 2002;93(3):1140–1151.PubMedGoogle Scholar
  18. 18.
    Strauer BE, Brehm M, Zeus T, et al. Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Dtsch Med Wochenschr 2001;126(34–35):932–938.PubMedCrossRefGoogle Scholar
  19. 19.
    Murry CE, Soonpaa MH, Reinecke H, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004;428(6983):664–668.PubMedCrossRefGoogle Scholar
  20. 20.
    Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 2004;428(6983):668–673.PubMedCrossRefGoogle Scholar
  21. 21.
    Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998;282(5391):1145–1147.PubMedCrossRefGoogle Scholar
  22. 22.
    Scholer HR, Ciesiolka T, Gruss P. A nexus between Oct-4 and E1A: implications for gene regulation in embryonic stem cells. Cell 1991;66(2):291–304.PubMedCrossRefGoogle Scholar
  23. 23.
    Pesce M, Scholer HR. Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells 2001;19(4):271–278.PubMedCrossRefGoogle Scholar
  24. 24.
    Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981;292(5819):154–156.PubMedCrossRefGoogle Scholar
  25. 25.
    Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 1981;78(12):7634–7638.PubMedCrossRefGoogle Scholar
  26. 26.
    Sissman NJ. Developmental landmarks in cardiac morphogenesis: comparative chronology. Am J Cardiol 1970;25(2):141–148.PubMedCrossRefGoogle Scholar
  27. 27.
    Wobus AM, Wallukat G, Hescheler J. Pluripotent mouse embryonic stem cells are able to differentiate into cardiomyocytes expressing chronotropic responses to adrenergic and cholinergic agents and Ca2+ channel blockers. Differentiation 1991;48:173–182.PubMedCrossRefGoogle Scholar
  28. 28.
    Maltsev VA, Rohwedel J, Hescheler J, et al. Embryonic stem cells differentiate in vitro into cardiomyocytes representing sinusnodal, atrial and ventricular cell types. Mech Dev 1993;44(1):41–50.PubMedCrossRefGoogle Scholar
  29. 29.
    Klug MG, Soonpaa MH, Field LJ. DNA synthesis and multinucleation in embryonic stem cell-derived cardiomyocytes. Am J Physiol 1995;269:H1913–H1921.PubMedGoogle Scholar
  30. 30.
    Klug MG, Soonpaa MH, Koh GY, Field LJ. Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J Clin Invest 1996;98:216–224.PubMedCrossRefGoogle Scholar
  31. 31.
    Westfall MV, Samuelson LC, Metzger JM. Troponin I isoform expression is developmentally regulated in differentiating embryonic stem cell-derived cardiac myocytes. Dev Dyn 1996;206:24–38.PubMedCrossRefGoogle Scholar
  32. 32.
    Westfall MV, Pasyk KA, Yule DI, et al. Ultrastructure and cell-cell coupling of cardiac myocytes differentiating in embryonic stem cell cultures. Cell Motil Cytoskeleton 1997;36:43–54.PubMedCrossRefGoogle Scholar
  33. 33.
    Kilborn MJ, Fedida D. A study of the developmental changes in outward currents of rat ventricular myocytes. J Physiol (Lond) 1990;430:37–0.Google Scholar
  34. 34.
    Rohwedel J, Maltsev V, Bober E, et al. 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 1994;164(1):87–101.PubMedCrossRefGoogle Scholar
  35. 35.
    Kehat I, Kenyagin-Karsenti D, Snir M, et al. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 2001;108(3):407–414.PubMedCrossRefGoogle Scholar
  36. 36.
    Xu C, Police S, Rao N, et al. Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res 2002;91(6):501–508.PubMedCrossRefGoogle Scholar
  37. 37.
    Spradling A, Drummond-Barbosa D, Kai T. Stem cells find their niche. Nature 2001;414(6859):98–104.PubMedCrossRefGoogle Scholar
  38. 38.
    Smith AG. Culture and differentiation of embryonic stem cells. J Tissue Culture Methods 1991;13:89–94.CrossRefGoogle Scholar
  39. 39.
    Wobus AM, Kaomei G, Shan J, et al. Retinoic acid accelerates embryonic stem cell-derived cardiac differentiation and enhances development of ventricular cardiomyocytes. J Mol Cell Cardiol 1997;29(6):1525–1539.PubMedCrossRefGoogle Scholar
  40. 40.
    Boheler KR, Czyz J, Tweedie D, et al. Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res 2002;91(3):189–201.PubMedCrossRefGoogle Scholar
  41. 41.
    Hidaka K, Lee JK, Kim HS, et al. Chamber-specific differentiation of Nkx2.5-positive cardiac precursor cells from murine embryonic stem cells. FASEB J 2003;17(6):740–742.PubMedGoogle Scholar
  42. 42.
    Chen Y, Yang Y, Rana JS, et al. Effects of vascular endothelial growth factor on proliferation and differentiation of embryonic stem cells. J Am Coll Cardiol 2003;41(6, Suppl A):273A.Google Scholar
  43. 43.
    Behfar A, Zingman LV, Hodgson DM, et al. Stem cell differentiation requires a paracrine pathway in the heart. FASEB J 2002;16(12):1558–1566.PubMedCrossRefGoogle Scholar
  44. 44.
    Schuldiner M, Yanuka O, Itskovitz-Eldor J, et al. From the cover: effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc Natl Acad Sci USA 2000;97(21):11307–11312.PubMedCrossRefGoogle Scholar
  45. 45.
    Connold AL, Frischknecht R, Vrbova G. Survival of embryonic cardiac myocytes transplanted into host rat soleus muscle. J Muscle Res Cell Motil 1995;16(5):481–489.PubMedCrossRefGoogle Scholar
  46. 46.
    Roell W, Lu ZJ, Bloch W, et al. Cellular cardiomyoplasty improves survival after myocardial injury. Circulation 2002;105(20):2435–2441.PubMedCrossRefGoogle Scholar
  47. 47.
    Connold AL, Frischknecht R, Dimitrakos M, et al. The survival of embryonic cardiomyocytes transplanted into damaged host rat myocardium. J Muscle RESC Motil 1997;18(1):63–70.CrossRefGoogle Scholar
  48. 48.
    Etzion S, Battler A, Barbash IM, et al. Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in rat model of extensive myocardial infarction. J Mol Cell Cardiol 2001;33:1321–1330.PubMedCrossRefGoogle Scholar
  49. 49.
    Feldman AM, McNamara D. Myocarditis. N Engl J Med 2000;343:1388–1398.PubMedCrossRefGoogle Scholar
  50. 50.
    Silver MA, Kowalczyk D. Coronary microvascular narrowing in acute murine Coxsackie B3 myocarditis. Am Heart J 1989;118:173–174.PubMedCrossRefGoogle Scholar
  51. 51.
    Kawai C. From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death-learning from the past for the future. Circulation 1999;99:1091–1100.PubMedGoogle Scholar
  52. 52.
    Wang JF, Yang Y, Wang G, et al. Embryonic stem cells attenuate viral myocarditis in murine model. Cell Transplant 2002;11(8):753–758.PubMedGoogle Scholar
  53. 53.
    Yechiel E, Barenholz Y, Henis YI. Lateral mobility and organization of phospholipids and proteins in rat myocyte membranes. Effects of aging and manipulation of lipid composition. J Biol Chem 1985;260(16):9132–9136.PubMedGoogle Scholar
  54. 54.
    Lieber S, Pain J, Diaz G, et al. Aging increases stiffness of cardiac myocytes measured by atomic force microscopy. Circulation 2003;108(17):IV–276.Google Scholar
  55. 55.
    Min JY, Malek S, Chen Y, et al. Stem cell therapy in aging hearts: myogenesis vs angiogenesis. Circulation 2003;108(17):IV–276.Google Scholar
  56. 56.
    Perez-Terzic C, Behfar A, Mery A, et al. Structural adaptation of the nuclear pore complex in stem cell-derived cardiomyocytes. Circ Res 2003;92(4):444–452.PubMedCrossRefGoogle Scholar
  57. 57.
    Mummery C, Ward D, van den Brink CE, et al. Cardiomyocyte differentiation of mouse and human embryonic stem cells. J Anat 2002;200(Pt 3):233–242.PubMedCrossRefGoogle Scholar
  58. 58.
    Vittet D, Prandini MH, Berthier R, et al. Embryonic stem cells differentiate in vitro to endothelial cells through successive maturation steps. Blood 1996;88(9):3424–3431.PubMedGoogle Scholar
  59. 59.
    Hirashima M, Kataoka H, Nishikawa S, et al. Maturation of embryonic stem cells into endothelial cells in an in vitro model of vasculogenesis. Blood 1999;93(4):1253–1263.PubMedGoogle Scholar
  60. 60.
    Yamashita J, Itoh H, Hirashima M, et al. Flk 1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 2000;408(6808):92–96.PubMedCrossRefGoogle Scholar
  61. 61.
    Yurugi-Kobayashi T, Itoh H, Yamashita J, et al. Effective contribution of transplanted vascular progenitor cells derived from embryonic stem cells to adult neovascularization in proper differentiation stage. Blood 2003;101(7):2675–2678.PubMedCrossRefGoogle Scholar
  62. 62.
    Van Meter CH, Claycomb WC Jr, Delcarpio JB, et al. Myoblast transplantation in the porcine model: a potential technique for myocardial repair. J Thorac Cardiovasc Surg 1995;110:1142–1148.Google Scholar
  63. 63.
    Watanabe E, Smith DM Jr, Delcarpio JB, et al. Cardiomyocyte transplantation in a porcine myocardial infarction model. Cell Transplant 1998;7:239–246.PubMedCrossRefGoogle Scholar
  64. 64.
    Tomita S, Mickle DA, Weisel RD, et al. Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg 2002;123(6):1132–1140.PubMedCrossRefGoogle Scholar
  65. 65.
    Kim EJ, Li RK, Weisel RD, et al. Angiogenesis by endothelial cell transplantation. J Thorac Cardiovasc Surg 2001;122(5):963–971.PubMedCrossRefGoogle Scholar
  66. 66.
    Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 2001;98(18):10344–10349.PubMedCrossRefGoogle Scholar
  67. 67.
    Li D, Zhao L, Liu M, et al. Kinetics of tumor necrosis factor alpha in plasma and the cardioprotective effect of a monoclonal antibody to tumor necrosis factor alpha in acute myocardial infarction. Am. Heart J 1999;137:1145–1152.PubMedCrossRefGoogle Scholar
  68. 68.
    Maury CP, Teppo AM. Circulating tumour necrosis factor-alpha (cachectin) in myocardial infarction. J Intern Med 1989;225:333–336.PubMedCrossRefGoogle Scholar
  69. 69.
    Halawa B, Salomon P, Jolda-Mydlowska B, et al. Levels of tumor necrosis factor (TNF-alpha) and interleukin 6 (IL-6) in serum of patients with acute myocardial infarction. Pol. Arch Med Wewn 1999;101:197–203.PubMedGoogle Scholar
  70. 70.
    Irwin MW, Mak S, Mann DL, et al. Tissue expression and immunolocalization of tumor necrosis factor-alpha in postinfarction dysfunctional myocardium. Circulation 1999;99:1492–1498.PubMedGoogle Scholar
  71. 71.
    Chen Y, Ke Q, Yang Y, et al. Cardiomyocytes overexpressing TNF-alpha attract migration of embryonic stem cells via activation of p38 and c-Jun amino-terminal kinase. FASEB J 2003;17(15):2231–2239.PubMedCrossRefGoogle Scholar
  72. 72.
    Kaplan E, Chen Y, Min JY, et al. Intracellular calcium regulates tumor necrosis factor-alpha-induced embryonic stem cell migration. Circulation 2004;43(5-Suppl A):270A.Google Scholar
  73. 73.
    Saito T, Kuang JQ, Bittira B, et al. Xenotransplant cardiac chimera: immune tolerance of adult stem cells. Ann Thorac Surg 2002;74(1):19–24.PubMedCrossRefGoogle Scholar
  74. 74.
    Fandrich F, Dresske B, Bader M, et al. Embryonic stem cells share immune-privileged features relevant for tolerance induction. J Mol Med 2002;80(6):343–350.PubMedCrossRefGoogle Scholar
  75. 75.
    Matzinger P. An innate sense of danger. Ann NY Acad Sci 2002;961:341–342.PubMedCrossRefGoogle Scholar
  76. 76.
    Matzinger P. The danger model: a renewed sense of self. Science 2002;296(5566):301–305.PubMedCrossRefGoogle Scholar
  77. 77.
    Anderson CC, Matzinger P. Danger: the view from the bottom of the cliff. Semin Immunol 2000;12(3):231–238.PubMedCrossRefGoogle Scholar
  78. 78.
    Toma C, Pittenger MF, Cahill KS, et al. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 2002;105:93–98.PubMedCrossRefGoogle Scholar
  79. 79.
    Fandrich F, Lin X, Chai GX, et al. Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning. Nat Med 2002;8:171–178.PubMedCrossRefGoogle Scholar
  80. 80.
    Morris PJ. The immunobiology of cell transplantation. Cell Transplant 1993;2:7–12.Google Scholar
  81. 81.
    O’Shea KS. Embryonic stem cell models of development. Anatom Rec 1999;257:32–41.CrossRefGoogle Scholar
  82. 82.
    Beschorner WE, Sudan DL, Radio SJ, et al. Heart xenograft survival with chimeric pig donors and modest immune suppression. Ann Surg 2003;237:265–272.PubMedCrossRefGoogle Scholar
  83. 83.
    Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature 1953;172:603–606.PubMedCrossRefGoogle Scholar
  84. 84.
    Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002;30:42–48.PubMedCrossRefGoogle Scholar
  85. 85.
    Strom TB, Field LJ, Ruediger M. Allogeneic stem cells, clinical transplantation, and the origins of regenerative medicine. Transplant Proc 2001;33:3044–3049.PubMedCrossRefGoogle Scholar
  86. 86.
    Ildstad ST, Wren SM, Boggs SS, et al. Cross-species bone marrow transplantation: evidence for tolerance induction, stem cell engraftment, and maturation of T lymphocytes in a xenogeneic stromal environment (rat-mouse). J Exp Med 1991;174:467–478.PubMedCrossRefGoogle Scholar
  87. 87.
    Wu G, Korsgren O, van Rooijen N, et al. Suppression of T cells results in long-term survival of mouse heart xenografts in C6-deficient rats. Xenotransplantation 2001;8:303–309.PubMedCrossRefGoogle Scholar
  88. 88.
    Xiao YF, Min JY, Morgan JP. Immunosuppression and xenotransplantation of cells for cardiac repair. Ann Thorac Surg 2004;77(2):737–744.PubMedCrossRefGoogle Scholar
  89. 89.
    Chen Y, He ZX, Liu A, et al. Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Res 2003;13(4):251–263.PubMedCrossRefGoogle Scholar
  90. 90.
    Hwang WS, Ryu YJ, Park JH, et al. Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science 2004;303(5664):1669–1674.PubMedCrossRefGoogle Scholar
  91. 91.
    Ventura C, Maioli M, Asara Y, et al. Butyric and retinoic mixed ester of hyaluronan: A novel differentiating glycoconjugate affording a high-throughput of cardiogenesis in embryonic stem cells. J Biol Chem 2004;279:23574–23579.PubMedCrossRefGoogle Scholar
  92. 92.
    Sachinidis A, Gissel C, Nierhoff D, et al. Identification of plateled-derived growth factor-BB as cardiogenesis-inducing factor in mouse embryonic stem cells under serum-free conditions. Cell Physiol Biochem 2003;13(6):423–429.PubMedCrossRefGoogle Scholar
  93. 93.
    Ventura C, Zinellu E, Maninchedda E, et al. Dynorphin B is an agonist of nuclear opioid receptors coupling nuclear protein kinase C activation to the transcription of cardiogenic genes in GTR1 embryonic stem cells. Circ Res 2003;92(6):623–629.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Yong-Fu Xiao
    • 1
  • Jiang-Yong Min
    • 1
  • James P. Morgan
    • 1
  1. 1.Cardiovascular Division, Department of MedicineBeth Israel Deaconess Medical Center and Harvard Medical SchoolBoston

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