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Stem-cell-based therapy and lessons from the heart

Nature volume 453, pages 322–329 (2008)Cite this article

Abstract

The potential usefulness of human embryonic stem cells for therapy derives from their ability to form any cell in the body. This potential has been used to justify intensive research despite some ethical concerns. In parallel, scientists have searched for adult stem cells that can be used as an alternative to embryonic cells, and, for the heart at least, these efforts have led to promising results. However, most adult cardiomyocytes are unable to divide and form new cardiomyocytes and would therefore be unable to replace those lost as a result of disease. Basic questions — for example, whether cardiomyocyte replacement or alternatives, such as providing the damaged heart with new blood vessels or growth factors to activate resident stem cells, are the best approach — remain to be fully addressed. Despite this, preclinical studies on cardiomyocyte transplantation in animals and the first clinical trials with adult stem cells have recently been published with mixed results.

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Figure 1: Transplantation strategy for cardiac repair.
Figure 2: A graft derived from human ES cells and extracellular-matrix production in a mouse heart.

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References

  1. Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Draper, J. S. et al. Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nature Biotechnol. 22, 53–54 (2004).

    CAS  Google Scholar 

  3. Wu, S., Chien, K. & Mummery, C. Origin and biology of nultipotent cardiovascular progenitor cells. Reverse translational medicine towards models of human heart disease. Cell 132, 537–543 (2008). This review describes the origin and fate of cardiac progenitor cells in embryonic and adult hearts, as well as those derived from ES cells.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Massberg, S. et al. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell 131, 994–1008 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Pouly, J. et al. Cardiac stem cells in the real world. J. Thorac. Cardiovasc. Surg. 135, 673–678 (2007).

    Google Scholar 

  6. Wu, S. M. et al. Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell 127, 1137–1150 (2006). This paper describes the molecular identity of Kit+NKX2-5+ progenitor cells in the heart and traces their fate during development in mice.

    CAS  PubMed  Google Scholar 

  7. Moretti, A. et al. Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127, 1151–1165 (2006). This paper describes genetic fate-mapping studies and shows that expression of Isl1, Nkx2-5 and Kdr defines multipotent cardiovascular progenitor cells, which can give rise to endothelial cells, cardiomyocytes and smooth muscle cells.

    CAS  PubMed  Google Scholar 

  8. Brazelton, T. R., Rossi, F. M., Keshet, G. I. & Blau, H. M. From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290, 1775–1779 (2000).

    ADS  CAS  PubMed  Google Scholar 

  9. Orlic, D. et al. Bone marrow cells regenerate infarcted myocardium. Nature 410, 701–705 (2001).

    ADS  CAS  PubMed  Google Scholar 

  10. Guan, K. & Hasenfuss, G. Do stem cells in the heart truly differentiate into cardiomyocytes? J. Mol. Cell Cardiol. 43, 377–387 (2007).

    CAS  PubMed  Google Scholar 

  11. Assmus, B. et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N. Engl. J. Med. 355, 1222–1232 (2006).

    CAS  PubMed  Google Scholar 

  12. Schachinger, V. et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N. Engl. J. Med. 355, 1210–1221 (2006).

    CAS  PubMed  Google Scholar 

  13. Lunde, K. et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N. Engl. J. Med. 355, 1199–1209 (2006).

    CAS  PubMed  Google Scholar 

  14. Janssens, S. et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 367, 113–121 (2006).

    PubMed  Google Scholar 

  15. Cintron, G., Johnson, G., Francis, G., Cobb, F. & Cohn, J. N. Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. Circulation 87, VI17–VI23 (1993).

    CAS  PubMed  Google Scholar 

  16. Adler, E. D. & Maddox, T. M. Cell therapy for cardiac disease: where do we go from here? Nature Clin. Pract. Cardiovasc. Med. 4, 2–3 (2007).

    Google Scholar 

  17. Lunde, K. et al. Exercise capacity and quality of life after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: results from the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) randomized controlled trial. Am. Heart J. 154, 710–718 (2007).

    PubMed  Google Scholar 

  18. Schachinger, V., Tonn, T., Dimmeler, S. & Zeiher, A. M. Bone-marrow-derived progenitor cell therapy in need of proof of concept: design of the REPAIR-AMI trial. Nature Clin. Pract. Cardiovasc. Med. 3 (Suppl. 1), S23–S28 (2006).

    Google Scholar 

  19. Murry, C. E. et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428, 664–668 (2004).

    ADS  CAS  PubMed  Google Scholar 

  20. Balsam, L. B. et al. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428, 668–673 (2004). References 19 and 20 were the first studies to show that haematopoietic stem cells do not transdifferentiate into cardiomyocytes when transplanted into a mouse heart.

    ADS  CAS  PubMed  Google Scholar 

  21. Nygren, J. M. et al. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nature Med. 10, 494–501 (2004).

    CAS  PubMed  Google Scholar 

  22. van Laake, L. W. et al. Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction. Stem Cell Res. 1, 9–24 (2007). This paper showed an improvement in cardiac function at 4 weeks after transplantation of human ES-cell-derived cardiomyocytes into mice that had undergone a myocardial infarction; however, this effect was not sustained at 12 weeks compared with mice receiving human ES-cell-derived non-cardiomyocytes.

    PubMed  Google Scholar 

  23. Fazel, S. et al. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J. Clin. Invest. 116, 1865–1877 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Yoshioka, T. et al. Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34+ stem cells in a nonhuman primate model. Stem Cells 23, 355–364 (2005).

    CAS  PubMed  Google Scholar 

  25. Limbourg, F. P. et al. Haematopoietic stem cells improve cardiac function after infarction without permanent cardiac engraftment. Eur. J. Heart Fail. 7, 722–729 (2005).

    CAS  PubMed  Google Scholar 

  26. Feygin, J., Mansoor, A., Eckman, P., Swingen, C. & Zhang, J. Functional and bioenergetic modulations in the infarct border zone following autologous mesenchymal stem cell transplantation. Am. J. Physiol. Heart Circ. Physiol. 293, H1772–H1780 (2007).

    CAS  PubMed  Google Scholar 

  27. Amsalem, Y. et al. Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium. Circulation 116, I38–I45 (2007).

    CAS  PubMed  Google Scholar 

  28. Breitbach, M. et al. Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 110, 1362–1369 (2007).

    CAS  PubMed  Google Scholar 

  29. Rubart, M. & Field, L. J. Cardiac regeneration: repopulating the heart. Annu. Rev. Physiol. 68, 29–49 (2006).

    CAS  PubMed  Google Scholar 

  30. Gnecchi, M. et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nature Med. 11, 367–368 (2005).

    CAS  PubMed  Google Scholar 

  31. Pelacho, B. et al. Multipotent adult progenitor cell transplantation increases vascularity and improves left ventricular function after myocardial infarction. J. Tissue Eng. Regen. Med. 1, 51–59 (2007).

    CAS  PubMed  Google Scholar 

  32. Smart, N. et al. Thymosin β4 induces adult epicardial progenitor mobilization and neovascularization. Nature 445, 177–182 (2007).

    ADS  CAS  PubMed  Google Scholar 

  33. Winter, E. M. et al. Preservation of left ventricular function and attenuation of remodeling after transplantation of human epicardium-derived cells into the infarcted mouse heart. Circulation 116, 917–927 (2007).

    CAS  PubMed  Google Scholar 

  34. Lepilina, A. et al. A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Cell 127, 607–619 (2006).

    CAS  PubMed  Google Scholar 

  35. Leobon, B. et al. Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc. Natl Acad. Sci. USA 100, 7808–7811 (2003).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  36. Dellavalle, A. et al. Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nature Cell Biol. 9, 255–267 (2007).

    CAS  PubMed  Google Scholar 

  37. Roell, W. et al. Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature 450, 819–824 (2007).

    ADS  CAS  PubMed  Google Scholar 

  38. Liu, J., Fu, J. D., Siu, C. W. & Li, R. A. Functional sarcoplasmic reticulum for calcium-handling of human embryonic stem cell-derived cardiomyocytes: Insights for driven maturation. Stem Cells 25, 3038–3044 (2007).

    CAS  PubMed  Google Scholar 

  39. Reinecke, H., Zhang, M., Bartosek, T. & Murry, C. E. Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts. Circulation 100, 193–202 (1999).

    CAS  PubMed  Google Scholar 

  40. Miragoli, M., Salvarani, N. & Rohr, S. Myofibroblasts induce ectopic activity in cardiac tissue. Circ. Res. 101, 755–758 (2007).

    CAS  PubMed  Google Scholar 

  41. Ferreira, L. S. et al. Vascular progenitor cells isolated from human embryonic stem cells give rise to endothelial and smooth muscle like cells and form vascular networks in vivo. Circ. Res. 101, 286–294 (2007).

    CAS  PubMed  Google Scholar 

  42. Huang, H. et al. Differentiation of human embryonic stem cells into smooth muscle cells in adherent monolayer culture. Biochem. Biophys. Res. Commun. 351, 321–327 (2006).

    CAS  PubMed  Google Scholar 

  43. Levenberg, S., Golub, J. S., Amit, M., Itskovitz-Eldor, J. & Langer, R. Endothelial cells derived from human embryonic stem cells. Proc. Natl Acad. Sci. USA 99, 4391–4396 (2002).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kehat, I. et al. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J. Clin. Invest. 108, 407–414 (2001). This was the first paper to describe the formation of cardiomyocytes from human ES cells.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Mummery, C. et al. Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. Circulation 107, 2733–2740 (2003).

    CAS  PubMed  Google Scholar 

  46. He, J. Q., Ma, Y., Lee, Y., Thomson, J. A. & Kamp, T. J. Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ. Res. 93, 32–39 (2003).

    CAS  PubMed  Google Scholar 

  47. 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).

    CAS  PubMed  Google Scholar 

  48. Beqqali, A., Kloots, J., Ward-van Oostwaard, D., Mummery, C. & Passier, R. Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes. Stem Cells 24, 1956–1967 (2006).

    CAS  PubMed  Google Scholar 

  49. Passier, R. et al. Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures. Stem Cells 23, 772–780 (2005).

    CAS  PubMed  Google Scholar 

  50. Kehat, I. et al. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nature Biotechnol. 22, 1282–1289 (2004).

    CAS  Google Scholar 

  51. Xue, T. et al. Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers. Circulation 111, 11–20 (2005).

    PubMed  Google Scholar 

  52. Laflamme, M. A. et al. Formation of human myocardium in the rat heart from human embryonic stem cells. Am. J. Pathol. 167, 663–671 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Dai, W. et al. Survival and maturation of human embryonic stem cell-derived cardiomyocytes in rat hearts. J. Mol. Cell Cardiol. 43, 504–516 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Laflamme, M. A. et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nature Biotechnol. 25, 1015–1024 (2007). This paper showed that rodents that had undergone a myocardial infarction had improved cardiac function at 4 weeks after transplantation of human ES-cell-derived cardiomyocytes.

    CAS  Google Scholar 

  55. Leor, J. et al. Human embryonic stem cell transplantation to repair the infarcted myocardium. Heart 93, 1278–1284 (2007).

    PubMed  PubMed Central  Google Scholar 

  56. van Laake, L. W. et al. Monitoring of cell therapy and assessment of cardiac function using magnetic resonance imaging in a mouse model of myocardial infarction. Nature Protocols 2, 2551–2567 (2007).

    CAS  PubMed  Google Scholar 

  57. Rubart, M., Wang, E., Dunn, K. W. & Field, L. J. Two-photon molecular excitation imaging of Ca2+ transients in Langendorff-perfused mouse hearts. Am. J. Physiol. Cell Physiol. 284, C1654–C1668 (2003).

    CAS  PubMed  Google Scholar 

  58. Rubart, M. et al. Physiological coupling of donor and host cardiomyocytes after cellular transplantation. Circ. Res. 92, 1217–1224 (2003).

    ADS  CAS  PubMed  Google Scholar 

  59. Erdo, F. et al. Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke. J. Cereb. Blood Flow Metab. 23, 780–785 (2003).

    PubMed  Google Scholar 

  60. Zimmermann, W. H. et al. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nature Med. 12, 452–458 (2006). This paper showed that tissue engineering is an attractive prospect for cardiac repair.

    CAS  PubMed  Google Scholar 

  61. Feinberg, A. W. et al. Muscular thin films for building actuators and powering devices. Science 317, 1366–1370 (2007).

    ADS  CAS  PubMed  Google Scholar 

  62. Furuta, A. et al. Pulsatile cardiac tissue grafts using a novel three-dimensional cell sheet manipulation technique functionally integrates with the host heart, in vivo. Circ. Res. 98, 705–712 (2006).

    CAS  PubMed  Google Scholar 

  63. Moelker, A. D. et al. Intracoronary delivery of umbilical cord blood derived unrestricted somatic stem cells is not suitable to improve LV function after myocardial infarction in swine. J. Mol. Cell Cardiol. 42, 735–745 (2007).

    CAS  PubMed  Google Scholar 

  64. Wang, Z. Z. et al. Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo. Nature Biotechnol. 25, 317–318 (2007).

    CAS  Google Scholar 

  65. Sone, M. et al. Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration. Arterioscler. Thromb. Vasc. Biol. 27, 2127–2134 (2007).

    CAS  PubMed  Google Scholar 

  66. Cho, S. W. et al. Improvement of postnatal neovascularization by human embryonic stem cell derived endothelial-like cell transplantation in a mouse model of hindlimb ischemia. Circulation 116, 2409–2419 (2007).

    CAS  PubMed  Google Scholar 

  67. Caspi, O. et al. Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circ. Res. 100, 263–272 (2007).

    ADS  CAS  PubMed  Google Scholar 

  68. Lu, S. J. et al. Generation of functional hemangioblasts from human embryonic stem cells. Nature Methods 4, 501–509 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Tian, X., Woll, P. S., Morris, J. K., Linehan, J. L. & Kaufman, D. S. Hematopoietic engraftment of human embryonic stem cell-derived cells is regulated by recipient innate immunity. Stem Cells 24, 1370–1380 (2006).

    CAS  PubMed  Google Scholar 

  70. Narayan, A. D. et al. Human embryonic stem cell-derived hematopoietic cells are capable of engrafting primary as well as secondary fetal sheep recipients. Blood 107, 2180–2183 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. van Laake, L. W. et al. Endoglin has a crucial role in blood cell-mediated vascular repair. Circulation 114, 2288–2297 (2006).

    CAS  PubMed  Google Scholar 

  72. Goldman, S. Stem and progenitor cell-based therapy of the human central nervous system. Nature Biotechnol. 23, 862–871 (2005).

    CAS  Google Scholar 

  73. Shim, J. H. et al. Directed differentiation of human embryonic stem cells towards a pancreatic cell fate. Diabetologia 50, 1228–1238 (2007).

    CAS  PubMed  Google Scholar 

  74. Duan, Y. et al. Differentiation and enrichment of hepatocyte-like cells from human embryonic stem cells in vitro and in vivo. Stem Cells 25, 3058–3068 (2007).

    CAS  PubMed  Google Scholar 

  75. Huber, I. et al. Identification and selection of cardiomyocytes during human embryonic stem cell differentiation. FASEB J. 21, 2551–2563 (2007).

    CAS  PubMed  Google Scholar 

  76. Anderson, D. et al. Transgenic enrichment of cardiomyocytes from human embryonic stem cells. Mol. Ther. 15, 2027–2036 (2007).

    CAS  PubMed  Google Scholar 

  77. Zeng, L. et al. Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Circulation 115, 1866–1875 (2007).

    PubMed  Google Scholar 

  78. Jain, M. et al. Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction. Circulation 103, 1920–1927 (2001).

    CAS  PubMed  Google Scholar 

  79. Ghostine, S. et al. Long-term efficacy of myoblast transplantation on regional structure and function after myocardial infarction. Circulation 106, I131–I136 (2002).

    PubMed  Google Scholar 

  80. Menard, C. et al. Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: a preclinical study. Lancet 366, 1005–1012 (2005).

    PubMed  Google Scholar 

  81. Kolossov, E. et al. Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium. J. Exp. Med. 203, 2315–2327 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Caspi, O. et al. Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J. Am. Coll. Cardiol. 50, 1884–1893 (2007).

    PubMed  Google Scholar 

  83. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).

    CAS  PubMed  Google Scholar 

  84. Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).

    CAS  PubMed  Google Scholar 

  85. Yu, J. et al. Induced pluripotent stem cell lnes derived from human somatic cells. Science 318, 1917–1920 (2007).

    ADS  CAS  PubMed  Google Scholar 

  86. Nakagawa, M. et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature Biotechnol. 26, 101–106 (2007).

    Google Scholar 

  87. Hanna, J. et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318, 1920–1923 (2007).

    ADS  CAS  PubMed  Google Scholar 

  88. Beltrami, A. P. et al. Evidence that human cardiac myocytes divide after myocardial infarction. N. Engl. J. Med. 344, 1750–1757 (2001).

    CAS  PubMed  Google Scholar 

  89. Beltrami, A. P. et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114, 763–776 (2003).

    CAS  PubMed  Google Scholar 

  90. Oh, H. et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl Acad. Sci. USA 100, 12313–12318 (2003).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  91. Martin, C. M. et al. Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev. Biol. 265, 262–275 (2004).

    CAS  PubMed  Google Scholar 

  92. Murry, C. E., Reinecke, H. & Pabon, L. M. Regeneration gaps: observations on stem cells and cardiac repair. J. Am. Coll. Cardiol. 47, 1777–1785 (2006).

    PubMed  Google Scholar 

  93. Evans, S. M., Mummery, C. & Doevendans, P. A. Progenitor cells for cardiac repair. Semin. Cell Dev. Biol. 18, 153–160 (2007).

    CAS  PubMed  Google Scholar 

  94. Parmacek, M. S. & Epstein, J. A. Pursuing cardiac progenitors: regeneration redux. Cell 120, 295–298 (2005).

    CAS  PubMed  Google Scholar 

  95. Laugwitz, K. L. et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433, 647–653 (2005).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  96. Messina, E. et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ. Res. 95, 911–921 (2004).

    CAS  PubMed  Google Scholar 

  97. Smith, R. R. et al. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation 115, 896–908 (2007).

    PubMed  Google Scholar 

  98. Bearzi, C. et al. Human cardiac stem cells. Proc. Natl Acad. Sci. USA 104, 14068–14073 (2007).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  99. Quaini, F. et al. Chimerism of the transplanted heart. N. Engl. J. Med. 346, 5–15 (2002).

    PubMed  Google Scholar 

  100. Urbanek, K. et al. Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc. Natl Acad. Sci. USA 100, 10440–10445 (2003).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

R.P. and L.W.v.L. were supported by the European Community's Sixth Framework Programme (Heart Repair). ES Cell International provided the human ES3–GFP.

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Authors and Affiliations

  1. Hubrecht Institute, Developmental Biology and Stem Cell Research, Uppsalalaan 8, CT, 3584, Utrecht, The Netherlands

    Robert Passier, Linda W. van Laake & Christine L. Mummery

  2. Department of Anatomy and Embryology, Leiden University Medical Centre, Einthovenweg 20, Leiden, 2333, The Netherlands

    Robert Passier & Christine L. Mummery

  3. Division Heart and Lungs, University Medical Center Utrecht, Heidelberglaan 100, CX, 3584, Utrecht, The Netherlands

    Linda W. van Laake

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Correspondence should be addressed to C.L.M. (c.l.mummery@lumc.nl).

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Passier, R., van Laake, L. & Mummery, C. Stem-cell-based therapy and lessons from the heart. Nature 453, 322–329 (2008). https://doi.org/10.1038/nature07040

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