Skip to main content

Advertisement

Log in

Differentiation of Human Embryonic Stem Cells to Cardiomyocytes for In Vitro and In Vivo Applications

  • Review
  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

The ability of human embryonic stem cells to differentiate into spontaneously contracting cardiomyocyte-like cells has attracted substantial interest from the scientific community over the last decade. From having been difficult to control, human cardiomyogenesis in vitro is now becoming a process which, to a certain extent, can be effectively manipulated and directed. Although much research remains, new and improved protocols for guiding pluripotent stem cells to the cardiomyocyte lineage are accumulating in the scientific literature. However, the stem cell derived cardiomyocytes described to date, generally resemble immature embryonic/fetal cardiomyocytes, and they are in some functional and structural aspects different from adult cardiomyocytes. Thus, a future challenge will be to design strategies that eventually may allow the cells to reach a higher degree of maturation in vitro. Nevertheless, the cells which can be prepared using current protocols still have wide spread utility, and they have begun to find their way into the drug discovery platforms used in the pharmaceutical industry. In addition, stem cell derived cardiomyocytes and cardiac progenitors are anticipated to have a tremendous impact on how heart disease will be treated in the future. Here, we will discuss recent strategies for the generation of cardiomyocytes from human embryonic stem cells and recapitulate their features, as well as highlight some in vitro applications for the cells. Finally, opportunities in the area of cardiac regenerative medicine will be illustrated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Meyer, T., Sartipy, P., Blind, F., Leisgen, C., & Guenther, E. (2007). New cell models and assays in cardiac safety profiling. Expert Opinion on Drug Metabolism and Toxicology, 3, 507–517.

    Article  PubMed  CAS  Google Scholar 

  2. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.

    Article  PubMed  CAS  Google Scholar 

  3. Bongso, A., & Tan, S. (2005). Human blastocyst culture and derivation of embryonic stem cell lines. Stem Cell Review, 1, 87–98.

    Article  Google Scholar 

  4. Daley, G. Q. (2007). L, Auerbach JM, et al. Ethics. The ISSCR guidelines for human embryonic stem cell research. Science, 315, 603–604.

    Article  PubMed  CAS  Google Scholar 

  5. Ameen, C., Strehl, R., Bjorquist, P., Lindahl, A., Hyllner, J., & Sartipy, P. (2008). Human embryonic stem cells: current technologies and emerging industrial applications. Critical Reviews in Oncology/hematology, 65, 54–80.

    Article  PubMed  Google Scholar 

  6. Dimmeler, S., Burchfield, J., & Zeiher, A. M. (2008). Cell-based therapy of myocardial infarction. Arteriosclerosis, Thrombosis, and Vascular Biology, 28, 208–216.

    Article  PubMed  CAS  Google Scholar 

  7. Murry, C. E., Field, L. J., & Menasche, P. (2005). Cell-based cardiac repair: reflections at the 10-year point. Circulation, 112, 3174–3183.

    Article  PubMed  Google Scholar 

  8. Anversa, P., Leri, A., Rota, M., et al. (2007). Concise review: stem cells, myocardial regeneration, and methodological artifacts. Stem Cells, 25, 589–601.

    Article  PubMed  CAS  Google Scholar 

  9. Zhang, J., Wilson, G. F., Soerens, A. G., et al. (2009). Functional cardiomyocytes derived from human induced pluripotent stem cells. Circulation Research, 104, e30–e41.

    Article  PubMed  CAS  Google Scholar 

  10. Zwi, L., Caspi, O., Arbel, G., et al. (2009). Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation, 120, 1513–1523.

    Article  PubMed  CAS  Google Scholar 

  11. Bruneau, B. G. (2008). The developmental genetics of congenital heart disease. Nature, 451, 943–948.

    Article  PubMed  CAS  Google Scholar 

  12. Buckingham, M., Meilhac, S., & Zaffran, S. (2005). Building the mammalian heart from two sources of myocardial cells. Nature Reviews Genetics, 6, 826–835.

    Article  PubMed  CAS  Google Scholar 

  13. Mummery, C., van der Heyden, M. A., de Boer, T. P., et al. (2007). Cardiomyocytes from human and mouse embryonic stem cells. Methods in Molecular Medicine, 140, 249–272.

    Article  PubMed  CAS  Google Scholar 

  14. He, J. Q., January, C. T., Thomson, J. A., & Kamp, T. J. (2007). Human embryonic stem cell-derived cardiomyocytes: drug discovery and safety pharmacology. Expert Opinion on Drug Discovery, 2, 739–753.

    Article  CAS  Google Scholar 

  15. Murry, C. E., & Keller, G. (2008). Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell, 132, 661–680.

    Article  PubMed  CAS  Google Scholar 

  16. Torella, D., Indolfi, C., Goldspink, D. F., & Ellison, G. M. (2008). Cardiac stem cell-based myocardial regeneration: towards a translational approach. Cardiovascular and Hematological Agents in Medicinal Chemistry, 6, 53–59.

    Article  PubMed  CAS  Google Scholar 

  17. Xu, Y., Shi, Y., & Ding, S. (2008). A chemical approach to stem-cell biology and regenerative medicine. Nature, 453, 338–344.

    Article  PubMed  CAS  Google Scholar 

  18. Itskovitz-Eldor, J., Schuldiner, M., Karsenti, D., et al. (2000). Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Molecular Medicine, 6, 88–95.

    PubMed  CAS  Google Scholar 

  19. Kehat, I., Kenyagin-Karsenti, D., Snir, M., et al. (2001). Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. Journal of clinical investigation, 108, 407–414.

    PubMed  CAS  Google Scholar 

  20. Mummery, C., Ward-van Oostwaard, D., Doevendans, P., et al. (2003). Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. Circulation, 107, 2733–2740.

    Article  PubMed  CAS  Google Scholar 

  21. Graichen, R., Xu, X., Braam, S. R., et al. (2008). Enhanced cardiomyogenesis of human embryonic stem cells by a small molecular inhibitor of p38 MAPK. Differentiation, 76, 357–370.

    Article  PubMed  CAS  Google Scholar 

  22. Xu, X. Q., Graichen, R., Soo, S. Y., et al. (2008). Chemically defined medium supporting cardiomyocyte differentiation of human embryonic stem cells. Differentiation, 76, 958–970.

    PubMed  CAS  Google Scholar 

  23. Zaffran, S., & Frasch, M. (2002). Early signals in cardiac development. Circulation Research, 91, 457–469.

    Article  PubMed  CAS  Google Scholar 

  24. Olson, E. N. (2004). A decade of discoveries in cardiac biology. Nature Medicine, 10, 467–474.

    Article  PubMed  CAS  Google Scholar 

  25. Filipczyk, A. A., Passier, R., Rochat, A., & Mummery, C. L. (2007). Regulation of cardiomyocyte differentiation of embryonic stem cells by extracellular signalling. Cellular and Molecular Life Sciences, 64, 704–718.

    Article  PubMed  CAS  Google Scholar 

  26. Yoon, B. S., Yoo, S. J., Lee, J. E., You, S., Lee, H. T., & Yoon, H. S. (2006). Enhanced differentiation of human embryonic stem cells into cardiomyocytes by combining hanging drop culture and 5-azacytidine treatment. Differentiation, 74, 149–159.

    Article  PubMed  CAS  Google Scholar 

  27. Ng, E. S., Davis, R. P., Azzola, L., Stanley, E. G., & Elefanty, A. G. (2005). Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation. Blood, 106, 1601–1603.

    Article  PubMed  CAS  Google Scholar 

  28. Burridge, P. W., Anderson, D., Priddle, H., et al. (2007). Improved human embryonic stem cell embryoid body homogeneity and cardiomyocyte differentiation from a novel V-96 plate aggregation system highlights interline variability. Stem Cells, 25, 929–938.

    Article  PubMed  CAS  Google Scholar 

  29. Marvin, M. J., Di Rocco, G., Gardiner, A., Bush, S. M., & Lassar, A. B. (2001). Inhibition of Wnt activity induces heart formation from posterior mesoderm. Genes and Development, 15, 316–327.

    Article  PubMed  CAS  Google Scholar 

  30. Schneider, V. A., & Mercola, M. (2001). Wnt antagonism initiates cardiogenesis in Xenopus laevis. Genes and Development, 15, 304–315.

    Article  PubMed  CAS  Google Scholar 

  31. Klaus, A., & Birchmeier, W. (2009). Developmental signaling in myocardial progenitor cells: a comprehensive view of Bmp-and Wnt/beta-catenin signaling. Pediatric Cardiology, 30, 609–616.

    Article  PubMed  Google Scholar 

  32. Tran, T. H., Wang, X., Browne, C., et al. (2009). Wnt3a-induced mesoderm formation and cardiomyogenesis in human embryonic stem cells. Stem Cells, 27, 1869–1878.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  34. Laflamme, M. A., Chen, K. Y., Naumova, A. V., et al. (2007). Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nature Biotechnology, 25, 1015–1024.

    Article  PubMed  CAS  Google Scholar 

  35. Takahashi, T., Lord, B., Schulze, P. C., et al. (2003). Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes. Circulation, 107, 1912–1916.

    Article  PubMed  CAS  Google Scholar 

  36. Wu, X., Ding, S., Ding, Q., Gray, N. S., & Schultz, P. G. (2004). Small molecules that induce cardiomyogenesis in embryonic stem cells. Journal of the American Chemical Society, 126, 1590–1591.

    Article  PubMed  CAS  Google Scholar 

  37. Willems, E., Bushway, P. J., & Mercola, M. (2009). Natural and synthetic regulators of embryonic stem cell cardiogenesis. Pediatric Cardiology, 30, 635–642.

    Article  PubMed  Google Scholar 

  38. Passier, R., van Laake, L. W., & Mummery, C. L. (2008). Stem-cell-based therapy and lessons from the heart. Nature, 453, 322–329.

    Article  PubMed  CAS  Google Scholar 

  39. Bu, L., Jiang, X., Martin-Puig, S., et al. (2009). Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature, 460, 113–117.

    Article  PubMed  CAS  Google Scholar 

  40. Kattman, S. J., Huber, T. L., & Keller, G. M. (2006). Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. Developmental Cell, 11, 723–732.

    Article  PubMed  CAS  Google Scholar 

  41. Yang, L., Soonpaa, M. H., Adler, E. D., et al. (2008). Human cardiovascular progenitor cells develop from a KDR + embryonic-stem-cell-derived population. Nature, 453, 524–528.

    Article  PubMed  CAS  Google Scholar 

  42. Moretti, A., Caron, L., Nakano, A., et al. (2006). Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell, 127, 1151–1165.

    Article  PubMed  CAS  Google Scholar 

  43. Christoforou, N., Miller, R. A., Hill, C. M., Jie, C. C., McCallion, A. S., & Gearhart, J. D. (2008). Mouse ES cell-derived cardiac precursor cells are multipotent and facilitate identification of novel cardiac genes. Journal of clinical investigation, 118, 894–903.

    PubMed  CAS  Google Scholar 

  44. Xu, C., Police, S., Rao, N., & Carpenter, M. K. (2002). Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circulation Research, 91, 501–508.

    Article  PubMed  CAS  Google Scholar 

  45. Xu, C., Police, S., Hassanipour, M., & Gold, J. D. (2006). Cardiac bodies: a novel culture method for enrichment of cardiomyocytes derived from human embryonic stem cells. Stem Cells and Development, 15, 631–639.

    Article  PubMed  CAS  Google Scholar 

  46. Rust, W., Balakrishnan, T., & Zweigerdt, R. (2009). Cardiomyocyte enrichment from human embryonic stem cell cultures by selection of ALCAM surface expression. Regenerative Medicine, 4, 225–237.

    Article  PubMed  CAS  Google Scholar 

  47. Kolossov, E., Lu, Z., Drobinskaya, I., et al. (2005). Identification and characterization of embryonic stem cell-derived pacemaker and atrial cardiomyocytes. FASEB journal, 19, 577–579.

    PubMed  CAS  Google Scholar 

  48. Anderson, D., Self, T., Mellor, I. R., Goh, G., Hill, S. J., & Denning, C. (2007). Transgenic enrichment of cardiomyocytes from human embryonic stem cells. Molecular Theraphy, 15, 2027–2036.

    Article  CAS  Google Scholar 

  49. Huber, I., Itzhaki, I., Caspi, O., et al. (2007). Identification and selection of cardiomyocytes during human embryonic stem cell differentiation. Faseb Journal, 21, 2551–2563.

    Article  PubMed  CAS  Google Scholar 

  50. Fu JD, Jiang P, Rushing S, Liu J, Chiamvimonvat N, Li RA. Na+/Ca2+ exchanger is a determinant of excitation-contraction coupling in human embryonic stem cell-derived ventricular cardiomyocytes. Stem Cells Dev 2009.

  51. Xu, X. Q., Zweigerdt, R., Soo, S. Y., et al. (2008). Highly enriched cardiomyocytes from human embryonic stem cells. Cytotherapy, 10, 376–389.

    Article  PubMed  CAS  Google Scholar 

  52. Kita-Matsuo, H., Barcova, M., Prigozhina, N., et al. (2009). Lentiviral vectors and protocols for creation of stable hESC lines for fluorescent tracking and drug resistance selection of cardiomyocytes. PLoS ONE, 4, e5046.

    Article  PubMed  CAS  Google Scholar 

  53. Snir, M., Kehat, I., Gepstein, A., et al. (2003). Assessment of the ultrastructural and proliferative properties of human embryonic stem cell-derived cardiomyocytes. American Journal of Physiology Heart and Circulatory Physiology, 285, H2355–H2363.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  55. Satin, J., Kehat, I., Caspi, O., et al. (2004). Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes. Journal of physiology, 559, 479–496.

    Article  PubMed  CAS  Google Scholar 

  56. Dolnikov, K., Shilkrut, M., Zeevi-Levin, N., et al. (2005). Functional properties of human embryonic stem cell-derived cardiomyocytes. Annals of the New York Academy of Sciences, 1047, 66–75.

    Article  PubMed  CAS  Google Scholar 

  57. Sartiani, L., Bettiol, E., Stillitano, F., Mugelli, A., Cerbai, E., & Jaconi, M. E. (2007). Developmental changes in cardiomyocytes differentiated from human embryonic stem cells: a molecular and electrophysiological approach. Stem Cells, 25, 1136–1144.

    Article  PubMed  CAS  Google Scholar 

  58. Reppel, M., Boettinger, C., & Hescheler, J. (2004). Beta-adrenergic and muscarinic modulation of human embryonic stem cell-derived cardiomyocytes. Cell Physiology and Biochemistry, 14, 187–196.

    Article  CAS  Google Scholar 

  59. Norstrom, A., Akesson, K., Hardarson, T., Hamberger, L., Bjorquist, P., & Sartipy, P. (2006). Molecular and pharmacological properties of human embryonic stem cell-derived cardiomyocytes. Experimental Biology and Medicine (Maywood), 231, 1753–1762.

    Google Scholar 

  60. Binah, O., Dolnikov, K., Sadan, O., et al. (2007). Functional and developmental properties of human embryonic stem cells-derived cardiomyocytes. Journal of electrocardiology, 40, S192–S196.

    Article  PubMed  Google Scholar 

  61. Brito-Martins, M., Harding, S. E., & Ali, N. N. (2008). beta(1)-and beta(2)-adrenoceptor responses in cardiomyocytes derived from human embryonic stem cells: comparison with failing and non-failing adult human heart. British Journal of Pharmacology, 153, 751–759.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  63. Synnergren, J., Adak, S., Englund, M. C., et al. (2008). Cardiomyogenic gene expression profiling of differentiating human embryonic stem cells. Journal of biotechnology, 134, 162–170.

    Article  PubMed  CAS  Google Scholar 

  64. Synnergren J, Akesson K, Dahlenborg K, et al. Molecular signature of cardiomyocyte clusters derived from human embryonic stem cells. Stem Cells 2008.

  65. Cao, F., Wagner, R. A., Wilson, K. D., et al. (2008). Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes. PLoS ONE, 3, e3474.

    Article  PubMed  CAS  Google Scholar 

  66. Xu, X. Q., Soo, S. Y., Sun, W., & Zweigerdt, R. (2009). Global Expression Profile of Highly Enriched Cardiomyocytes Derived from Human Embryonic Stem Cells. Stem Cells, 27, 2163–2174.

    Article  PubMed  CAS  Google Scholar 

  67. Kola, I., & Landis, J. (2004). Can the pharmaceutical industry reduce attrition rates? Nature Reviews Drug Discovery, 3, 711–715.

    Article  PubMed  CAS  Google Scholar 

  68. Jonsson, M. K. B., van Veen, T. A. B., Goumans, M. J., Vos, M. A., Duker, G., & Sartipy, P. (2009). Improvement of cardiac efficacy and safety models in drug discovery by the use of stem cell-derived cardiomyocytes. Expert Opinion Drug Discovery, 4, 357–372.

    Article  CAS  Google Scholar 

  69. Kimes, B. W., & Brandt, B. L. (1976). Properties of a clonal muscle cell line from rat heart. Experimental Cell Research, 98, 367–381.

    Article  PubMed  CAS  Google Scholar 

  70. Claycomb, W. C., Lanson, N. A., Jr., Stallworth, B. S., et al. (1998). HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte. Proceedings of the National Academy of Sciences of the United States of America, 95, 2979–2984.

    Article  PubMed  CAS  Google Scholar 

  71. Reppel, M., Pillekamp, F., Brockmeier, K., et al. (2005). The electrocardiogram of human embryonic stem cell-derived cardiomyocytes. Journal of electrocardiology, 38, 166–170.

    Article  PubMed  Google Scholar 

  72. Caspi O, Itzhaki I, Arbel G, et al. In Vitro Electrophysiological Drug Testing using Human Embryonic Stem Cell Derived Cardiomyocytes. Stem Cells Dev 2008.

  73. Tanaka, T., Tohyama, S., Murata, M., et al. (2009). In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. Biochemical and Biophysical Research Communications, 385, 497–502.

    Article  PubMed  CAS  Google Scholar 

  74. Altena, R., Perik, P. J., van Veldhuisen, D. J., de Vries, E. G., & Gietema, J. A. (2009). Cardiovascular toxicity caused by cancer treatment: strategies for early detection. Lancet oncology, 10, 391–399.

    Article  PubMed  CAS  Google Scholar 

  75. Dolci, A., Dominici, R., Cardinale, D., Sandri, M. T., & Panteghini, M. (2008). Biochemical markers for prediction of chemotherapy-induced cardiotoxicity: systematic review of the literature and recommendations for use. American Journal of Clinical Pathology, 130, 688–695.

    Article  PubMed  CAS  Google Scholar 

  76. Kloner, R. A., & Jennings, R. B. (2001). Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 1. Circulation, 104, 2981–2989.

    Article  PubMed  CAS  Google Scholar 

  77. Braam SR, Denning C, van den Brink S, et al. Improved genetic manipulation of human embryonic stem cells. Nat Methods 2008.

  78. Sartipy, P., Olsson, B., Hyllner, J., & Synnergren, J. (2009). Regulation of 'stemness' and stem cell differentiation by microRNAs. IDrugs, 12, 492–496.

    PubMed  Google Scholar 

  79. Dimos, J. T., Rodolfa, K. T., Niakan, K. K., et al. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science, 321, 1218–1221.

    Article  PubMed  CAS  Google Scholar 

  80. Park, I. H., Arora, N., Huo, H., et al. (2008). Disease-specific induced pluripotent stem cells. Cell, 134, 877–886.

    Article  PubMed  CAS  Google Scholar 

  81. Bergmann, O., Bhardwaj, R. D., Bernard, S., et al. (2009). Evidence for cardiomyocyte renewal in humans. Science, 324, 98–102.

    Article  PubMed  CAS  Google Scholar 

  82. Kubo, H., Jaleel, N., Kumarapeli, A., et al. (2008). Increased cardiac myocyte progenitors in failing human hearts. Circulation, 118, 649–657.

    Article  PubMed  Google Scholar 

  83. Kehat, I., Khimovich, L., Caspi, O., et al. (2004). Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nature Biotechnology, 22, 1282–1289.

    Article  PubMed  CAS  Google Scholar 

  84. Laflamme, M. A., Gold, J., Xu, C., et al. (2005). Formation of human myocardium in the rat heart from human embryonic stem cells. American Journal of Pathology, 167, 663–671.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  86. Caspi, O., Huber, I., Kehat, I., et al. (2007). Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. Journal of the American College of Cardiology, 50, 1884–1893.

    Article  PubMed  Google Scholar 

  87. van Laake, L. W., Passier, R., Monshouwer-Kloots, J., et al. (2007). Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction. Stem Cell Research, 1, 9–24.

    PubMed  Google Scholar 

  88. van Laake LW, Passier R, den Ouden K, et al. Improvement of mouse cardiac function by hESC-derived cardiomyocytes correlates with vascularity but not graft size. Stem Cell Res 2009.

  89. Stevens, K. R., Pabon, L., Muskheli, V., & Murry, C. E. (2009). Scaffold-free human cardiac tissue patch created from embryonic stem cells. Tissue Engineering: Part A, 15, 1211–1222.

    Article  CAS  Google Scholar 

  90. Stevens, K. R., Kreutziger, K. L., Dupras, S. K., et al. (2009). Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue. Proceedings of the National Academy of Sciences of the United States of America, 106, 16568–16573.

    Article  PubMed  Google Scholar 

  91. Nelson, T. J., Martinez-Fernandez, A., Yamada, S., Perez-Terzic, C., Ikeda, Y., & Terzic, A. (2009). Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation, 120, 408–416.

    Article  PubMed  Google Scholar 

  92. Messina, E., De Angelis, L., Frati, G., et al. (2004). Isolation and expansion of adult cardiac stem cells from human and murine heart. Circulation Research, 95, 911–921.

    Article  PubMed  CAS  Google Scholar 

  93. Bearzi, C., Rota, M., Hosoda, T., et al. (2007). Human cardiac stem cells. Proceedings of the National Academy of Sciences of the United States of America, 104, 14068–14073.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  95. van Vliet, P., Roccio, M., Smits, A. M., et al. (2008). Progenitor cells isolated from the human heart: a potential cell source for regenerative therapy. Netherlands Heart Journal, 16, 163–169.

    PubMed  Google Scholar 

  96. Martin, C. M., Meeson, A. P., Robertson, S. M., et al. (2004). Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Developmental Biology, 265, 262–275.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  98. Chen, S., Zhang, Q., Wu, X., Schultz, P. G., & Ding, S. (2004). Dedifferentiation of lineage-committed cells by a small molecule. Journal of the American Chemical Society, 126, 410–411.

    Article  PubMed  CAS  Google Scholar 

  99. Thomas, R. J., Anderson, D., Chandra, A., et al. (2009). Automated, scalable culture of human embryonic stem cells in feeder-free conditions. Biotechnology and Bioengineering, 102, 1636–1644.

    Article  PubMed  CAS  Google Scholar 

  100. Goswami, J., & Rao, M. (2007). Embryonic stem cell therapy. IDrugs, 10, 713–719.

    PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported, in part, by the European Community’s FP6 contracts LSHM-CT-2005-018630 (“HeartRepair”) and LSHB-CT-2007-037636 (“InVitroHeart”).

Conflict of Interest

HV, JH, and PS are employed by Cellartis AB. Cellartis AB is Biotech company with commercial interests in stem cell technologies.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Sartipy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vidarsson, H., Hyllner, J. & Sartipy, P. Differentiation of Human Embryonic Stem Cells to Cardiomyocytes for In Vitro and In Vivo Applications. Stem Cell Rev and Rep 6, 108–120 (2010). https://doi.org/10.1007/s12015-010-9113-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-010-9113-x

Keywords

Navigation