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Cardiac Differentiation of Pluripotent Stem Cells

DOI: 10.4061/2011/383709

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Abstract:

The ability of human pluripotent stem cells to differentiate towards the cardiac lineage has attracted significant interest, initially with a strong focus on regenerative medicine. The ultimate goal to repair the heart by cardiomyocyte replacement has, however, proven challenging. Human cardiac differentiation has been difficult to control, but methods are improving, and the process, to a certain extent, can be manipulated and directed. The stem cell-derived cardiomyocytes described to date exhibit rather immature functional and structural characteristics compared to adult cardiomyocytes. Thus, a future challenge will be to develop strategies to reach a higher degree of cardiomyocyte maturation in vitro, to isolate cardiomyocytes from the heterogeneous pool of differentiating cells, as well as to guide the differentiation into the desired subtype, that is, ventricular, atrial, and pacemaker cells. In this paper, we will discuss the strategies for the generation of cardiomyocytes from pluripotent stem cells and their characteristics, as well as highlight some applications for the cells. 1. Introduction Human cardiomyocytes can be isolated from heart biopsies, but the access to human heart tissue is very limited, and the procedure is complicated; it is difficult to obtain viable cell preparations in large quantities, and the cells obtained do not beat spontaneously. Thus, physiologically relevant in vitro models for human cardiomyocytes are currently limited. This has led in the creation of alternative models, such as isolation of cardiomyocytes from various newborn animals or production of genetically engineered cell lines overexpressing certain target proteins (e.g., ion channels) [1]. All of these models, however, share significant limitations with respect to their basic physiological differences compared to human cardiomyocytes as well as high costs and ethical questions. A number of different human tissues have been proposed as the source of stem cells able to generate new cardiomyocytes (e.g., fetal cardiomyocytes, adult cardiac progenitor cells, skeletal myoblasts, bone marrow-derived stem cells, adipose-derived stem cells, umbilical cord-derived stem cells, and pluripotent stem cells) [2]. The cardiac differentiation potential of adult, multipotent, stem cells found in fetal and adult tissues, however, is controversial [3, 4]. This has been attributed to the limited plasticity of adult stem cells, which precludes their differentiation into functional cardiomyocytes. The only adult stem cells that clearly have the potential to differentiate into

References

[1]  T. Meyer, P. Sartipy, F. Blind, C. Leisgen, and E. Guenther, “New cell models and assays in cardiac safety profiling,” Expert Opinion on Drug Metabolism and Toxicology, vol. 3, no. 4, pp. 507–517, 2007.
[2]  S. Dimmeler, J. Burchfield, and A. M. Zeiher, “Cell-based therapy of myocardial infarction,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 2, pp. 208–216, 2008.
[3]  C. E. Murry, L. J. Field, and P. Menasché, “Cell-based cardiac repair reflections at the 10-year point,” Circulation, vol. 112, no. 20, pp. 3174–3183, 2005.
[4]  P. Anversa, A. Leri, M. Rota et al., “Concise review: stem cells, myocardial regeneration, and methodological artifacts,” Stem Cells, vol. 25, no. 3, pp. 589–601, 2007.
[5]  G. Blin, D. Nury, S. Stefanovic et al., “A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates,” Journal of Clinical Investigation, vol. 120, no. 4, pp. 1125–1139, 2010.
[6]  I. Kehat, D. Kenyagin-Karsenti, M. Snir et al., “Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes,” Journal of Clinical Investigation, vol. 108, no. 3, pp. 407–414, 2001.
[7]  C. Xu, S. Police, N. Rao, and M. K. Carpenter, “Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells,” Circulation Research, vol. 91, no. 6, pp. 501–508, 2002.
[8]  J. Q. He, Y. Ma, Y. Lee, J. A. Thomson, and T. J. Kamp, “Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization,” Circulation Research, vol. 93, no. 1, pp. 32–39, 2003.
[9]  C. Mummery, D. Ward-van Oostwaard, P. Doevendans et al., “Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells,” Circulation, vol. 107, no. 21, pp. 2733–2740, 2003.
[10]  C. Améen, R. Strehl, P. Bj?rquist, A. Lindahl, J. Hyllner, and P. Sartipy, “Human embryonic stem cells: current technologies and emerging industrial applications,” Critical Reviews in Oncology/Hematology, vol. 65, no. 1, pp. 54–80, 2008.
[11]  J. A. Thomson, “Embryonic stem cell lines derived from human blastocysts,” Science, vol. 282, no. 5391, pp. 1145–1147, 1998.
[12]  J. Zhang, G. F. Wilson, A. G. Soerens et al., “Functional cardiomyocytes derived from human induced pluripotent stem cells,” Circulation Research, vol. 104, no. 4, pp. e30–e41, 2009.
[13]  L. Zwi, O. Caspi, G. Arbel et al., “Cardiomyocyte differentiation of human induced pluripotent stem cells,” Circulation, vol. 120, no. 15, pp. 1513–1523, 2009.
[14]  A. Haase, R. Olmer, K. Schwanke et al., “Generation of induced pluripotent stem cells from human cord blood,” Cell Stem Cell, vol. 5, no. 4, pp. 434–441, 2009.
[15]  H. Vidarsson, J. Hyllner, and P. Sartipy, “Differentiation of human embryonic stem cells to cardiomyocytes for in vitro and in vivo applications,” Stem Cell Reviews and Reports, vol. 6, no. 1, pp. 108–120, 2010.
[16]  S. R. Braam, R. Passier, and C. L. Mummery, “Cardiomyocytes from human pluripotent stem cells in regenerative medicine and drug discovery,” Trends in Pharmacological Sciences, vol. 30, no. 10, pp. 536–545, 2009.
[17]  K. Takahashi, K. Tanabe, M. Ohnuki et al., “Induction of pluripotent stem cells from adult human fibroblasts by defined factors,” Cell, vol. 131, no. 5, pp. 861–872, 2007.
[18]  J. Yu, M. A. Vodyanik, K. Smuga-Otto et al., “Induced pluripotent stem cell lines derived from human somatic cells,” Science, vol. 318, no. 5858, pp. 1917–1920, 2007.
[19]  I. Itzhaki, L. Maizels, I. Huber, et al., “Modelling the long QT syndrome with induced pluripotent stem cells,” Nature, vol. 471, no. 7337, pp. 225–229, 2011.
[20]  A. Moretti, M. Bellin, A. Welling et al., “Patient-specific induced pluripotent stem-cell models for long-QT syndrome,” New England Journal of Medicine, vol. 363, no. 15, pp. 1397–1409, 2010.
[21]  I. Kehat, L. Khimovich, O. Caspi et al., “Electromechanical integration of cardiomyocytes derived from human embryonic stem cells,” Nature Biotechnology, vol. 22, no. 10, pp. 1282–1289, 2004.
[22]  M. A. Laflamme, J. Gold, C. Xu et al., “Formation of human myocardium in the rat heart from human embryonic stem cells,” American Journal of Pathology, vol. 167, no. 3, pp. 663–671, 2005.
[23]  J. Leor, S. Gerecht, S. Cohen et al., “Human embryonic stem cell transplantation to repair the infarcted myocardium,” Heart, vol. 93, no. 10, pp. 1278–1284, 2007.
[24]  O. Caspi, I. Huber, I. Kehat et al., “Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts,” Journal of the American College of Cardiology, vol. 50, no. 19, pp. 1884–1893, 2007.
[25]  L. W. van Laake, R. Passier, J. Monshouwer-Kloots et al., “Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction,” Stem Cell Research, vol. 1, no. 1, pp. 9–24, 2007.
[26]  W. Dai, L. J. Field, M. Rubart et al., “Survival and maturation of human embryonic stem cell-derived cardiomyocytes in rat hearts,” Journal of Molecular and Cellular Cardiology, vol. 43, no. 4, pp. 504–516, 2007.
[27]  M. A. Laflamme, K. Y. Chen, A. V. Naumova et al., “Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts,” Nature Biotechnology, vol. 25, no. 9, pp. 1015–1024, 2007.
[28]  T. J. Nelson, A. Martinez-Fernandez, S. Yamada, C. Perez-Terzic, Y. Ikeda, and A. Terzic, “Repair of acute myocardial infarction with induced pluripotent stem cells induced by human stemness factors,” Circulation, vol. 120, no. 5, pp. 408–416, 2009.
[29]  F. F. Yi, L. Yang, Y. H. Li, PI. X. Su, J. Cai, and X. C. Yang, “Electrophysiological development of transplanted embryonic stem cell-derived cardiomyocytes in the hearts of syngeneic mice,” Archives of Medical Research, vol. 40, no. 5, pp. 339–344, 2009.
[30]  Y. M. Zhang, C. Hartzell, M. Narlow, and S. C. Dudley Jr., “Stem cell-derived cardiomyocytes demonstrate arrhythmic potential,” Circulation, vol. 106, no. 10, pp. 1294–1299, 2002.
[31]  D. Srivastava and K. N. Ivey, “Potential of stem-cell-based therapies for heart disease,” Nature, vol. 441, no. 7097, pp. 1097–1099, 2006.
[32]  Y. Hiroi, S. Kudoh, K. Monzen et al., “Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation,” Nature Genetics, vol. 28, no. 3, pp. 276–280, 2001.
[33]  T. Peterkin, A. Gibson, and R. Patient, “GATA-6 maintains BMP-4 and Nkx2 expression during cardiomyocyte precursor maturation,” EMBO Journal, vol. 22, no. 16, pp. 4260–4273, 2003.
[34]  T. F. Plageman Jr. and K. E. Yutzey, “Differential expression and function of Tbx5 and Tbx20 in cardiac development,” Journal of Biological Chemistry, vol. 279, no. 18, pp. 19026–19034, 2004.
[35]  P. Riley, L. Anson-Cartwright, and J. C. Cross, “The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis,” Nature Genetics, vol. 18, no. 3, pp. 271–275, 1998.
[36]  A. J. Watt, M. A. Battle, J. Li, and S. A. Duncan, “GATA4 is essential for formation of the proepicardium and regulates cardiogenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 34, pp. 12573–12578, 2004.
[37]  A. Bondue, G. Lapouge, C. Paulissen et al., “Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification,” Cell stem cell, vol. 3, no. 1, pp. 69–84, 2008.
[38]  R. C. Lindsley, J. G. Gill, T. L. Murphy et al., “Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs,” Cell stem cell, vol. 3, no. 1, pp. 55–68, 2008.
[39]  M. J. Marvin, G. Di Rocco, A. Gardiner, S. M. Bush, and A. B. Lassar, “Inhibition of Wnt activity induces heart formation from posterior mesoderm,” Genes and Development, vol. 15, no. 3, pp. 316–327, 2001.
[40]  T. Mima, H. Ueno, D. A. Fischman, L. T. Williams, and T. Mikawa, “Fibroblast growth factor receptor is required for in vivo cardiac myocyte proliferation at early embryonic stages of heart development,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 2, pp. 467–471, 1995.
[41]  G. Winnier, M. Blessing, P. A. Labosky, and B. L. M. Hogan, “Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse,” Genes and Development, vol. 9, no. 17, pp. 2105–2116, 1995.
[42]  H. Zhang and A. Bradley, “Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development,” Development, vol. 122, no. 10, pp. 2977–2986, 1996.
[43]  A. E. Pasquinelli, S. Hunter, and J. Bracht, “MicroRNAs: a developing story,” Current Opinion in Genetics and Development, vol. 15, no. 2, pp. 200–205, 2005.
[44]  Y. Zhao and D. Srivastava, “A developmental view of microRNA function,” Trends in Biochemical Sciences, vol. 32, no. 4, pp. 189–197, 2007.
[45]  T. E. Callis, Z. Deng, J. F. Chen, and DA. Z. Wang, “Muscling through the microRNA world,” Experimental Biology and Medicine, vol. 233, no. 2, pp. 131–138, 2008.
[46]  E. van Rooij, N. Liu, and E. N. Olson, “MicroRNAs flex their muscles,” Trends in Genetics, vol. 24, no. 4, pp. 159–166, 2008.
[47]  Z. Wang, X. Luo, Y. Lu, and B. Yang, “miRNAs at the heart of the matter,” Journal of Molecular Medicine, vol. 86, no. 7, pp. 771–783, 2008.
[48]  K. N. Ivey, A. Muth, J. Arnold et al., “MicroRNA regulation of cell lineages in mouse and human embryonic stem cells,” Cell Stem Cell, vol. 2, no. 3, pp. 219–229, 2008.
[49]  D. Nury, T. Neri, and M. Pucéat, “Human embryonic stem cells and cardiac cell fate,” Journal of Cellular Physiology, vol. 218, no. 3, pp. 455–459, 2009.
[50]  P. Gadue, T. L. Huber, P. J. Paddison, and G. M. Keller, “Wnt and TGF-β signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 45, pp. 16806–16811, 2006.
[51]  R. C. Lindsley, J. G. Gill, M. Kyba, T. L. Murphy, and K. M. Murphy, “Canonical Wnt signaling is required for development of embryonic stem cell-derived mesoderm,” Development, vol. 133, no. 19, pp. 3787–3796, 2006.
[52]  A. C. Foley, O. Korol, A. M. Timmer, and M. Mercola, “Multiple functions of Cerberus cooperate to induce heart downstream of Nodal,” Developmental Biology, vol. 303, no. 1, pp. 57–65, 2007.
[53]  A. C. Foley and M. Mercola, “Heart induction by Wnt antagonists depends on the homeodomain transcription factor Hex,” Genes and Development, vol. 19, no. 3, pp. 387–396, 2005.
[54]  V. A. Schneider and M. Mercola, “Wnt antagonism initiates cardiogenesis in Xenopus laevis,” Genes and Development, vol. 15, no. 3, pp. 304–315, 2001.
[55]  A. T. Naito, I. Shiojima, H. Akazawa et al., “Developmental stage-specific biphasic roles of Wnt/β-catenin signaling in cardiomyogenesis and hematopoiesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 52, pp. 19812–19817, 2006.
[56]  S. Ueno, G. Weidinger, T. Osugi et al., “Biphasic role for Wnt/β-catenin signaling in cardiac specification in zebrafish and embryonic stem cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 23, pp. 9685–9690, 2007.
[57]  L. Yang, M. H. Soonpaa, E. D. Adler et al., “Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population,” Nature, vol. 453, no. 7194, pp. 524–528, 2008.
[58]  V. C. Chen, R. Stull, D. Joo, X. Cheng, and G. Keller, “Notch signaling respecifies the hemangioblast to a cardiac fate,” Nature Biotechnology, vol. 26, no. 10, pp. 1169–1178, 2008.
[59]  J. Itskovitz-Eldor, M. Schuldiner, D. Karsenti et al., “Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers,” Molecular Medicine, vol. 6, no. 2, pp. 88–95, 2000.
[60]  T. H. Tran, X. Wang, C. Browne et al., “Wnt3a-induced mesoderm formation and cardiomyogenesis in human embryonic stem cells,” Stem Cells, vol. 27, no. 8, pp. 1869–1878, 2009.
[61]  B. S. Yoon, S. J. Yoo, J. E. Lee, S. You, H. T. Lee, and H. S. Yoon, “Enhanced differentiation of human embryonic stem cells into cardiomyocytes by combining hanging drop culture and 5-azacytidine treatment,” Differentiation, vol. 74, no. 4, pp. 149–159, 2006.
[62]  E. S. Ng, R. P. Davis, L. Azzola, E. G. Stanley, and A. G. Elefanty, “Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation,” Blood, vol. 106, no. 5, pp. 1601–1603, 2005.
[63]  S. Niebruegge, C. L. Bauwens, R. Peerani et al., “Generation of human embryonic stem cell-derived mesoderm and cardiac cells using size-specified aggregates in an oxygen-controlled bioreactor,” Biotechnology and Bioengineering, vol. 102, no. 2, pp. 493–507, 2009.
[64]  E. Serena, E. Figallo, N. Tandon et al., “Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species,” Experimental Cell Research, vol. 315, no. 20, pp. 3611–3619, 2009.
[65]  J. Synnergren, K. ?kesson, K. Dahlenborg et al., “Molecular signature of cardiomyocyte clusters derived from human embryonic stem cells,” Stem Cells, vol. 26, no. 7, pp. 1831–1840, 2008.
[66]  F. Cao, R. A. Wagner, K. D. Wilson et al., “Transcriptional and functional profilling of human embryonic stem cell-derived cardiomyocytes,” PLoS One, vol. 3, no. 10, Article ID e3474, 2008.
[67]  X. Q. Xu, S. Y. Soo, W. Sun, and R. Zweigerdt, “Global expression profile of highly enriched cardiomyocytes derived from human embryonic stem cells,” Stem Cells, vol. 27, no. 9, pp. 2163–2174, 2009.
[68]  R. Passier, D. Ward-Van Oostwaard, J. Snapper et al., “Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures,” Stem Cells, vol. 23, no. 6, pp. 772–780, 2005.
[69]  E. Willems, P. J. Bushway, and M. Mercola, “Natural and synthetic regulators of embryonic stem cell cardiogenesis,” Pediatric Cardiology, vol. 30, no. 5, pp. 635–642, 2009.
[70]  C. Freund, R. P. Davis, K. Gkatzis, D. Ward-van Oostwaard, and C. L. Mummery, “The first reported generation of human induced pluripotent stem cells (iPS cells) and iPS cell-derived cardiomyocytes in the Netherlands,” Netherlands Heart Journal, vol. 18, no. 1, pp. 51–54, 2010.
[71]  R. Graichen, X. Xu, S. R. Braam et al., “Enhanced cardiomyogenesis of human embryonic stem cells by a small molecular inhibitor of p38 MAPK,” Differentiation, vol. 76, no. 4, pp. 357–370, 2008.
[72]  C. Freund, D. W. V. Oostwaard, J. Monshouwer-Kloots et al., “Insulin redirects differentiation from cardiogenic mesoderm and endoderm to neuroectoderm in differentiating human embryonic stem cells,” Stem Cells, vol. 26, no. 3, pp. 724–733, 2008.
[73]  X. Q. Xu, R. Graichen, S. Y. Soo et al., “Chemically defined medium supporting cardiomyocyte differentiation of human embryonic stem cells,” Differentiation, vol. 76, no. 9, pp. 958–970, 2008.
[74]  Y. Kang, J. M. Nagy, J. M. Polak, and A. Mantalaris, “Proteomic characterization of the conditioned media produced by the visceral endoderm-like cell lines HepG2 and END2: toward a defined medium for the osteogenic/chondrogenic differentiation of embryonic stem cells,” Stem Cells and Development, vol. 18, no. 1, pp. 77–92, 2009.
[75]  D. K. Arrell, N. J. Niederl?nder, R. S. Faustino, A. Behfar, and A. Terzic, “Cardioinductive network guiding stem cell differentiation revealed by proteomic cartography of tumor necrosis factor α-primed endodermal secretome,” Stem Cells, vol. 26, no. 2, pp. 387–400, 2008.
[76]  T. G. Otsuji, I. Minami, Y. Kurose, K. Yamauchi, M. Tada, and N. Nakatsuji, “Progressive maturation in contracting cardiomyocytes derived from human embryonic stem cells: qualitative effects on electrophysiological responses to drugs,” Stem Cell Research, vol. 4, no. 3, pp. 201–213, 2010.
[77]  C. Xu, S. Police, M. Hassanipour, and J. D. Gold, “Cardiac bodies: a novel culture method for enrichment of cardiomyocytes derived from human embryonic stem cells,” Stem Cells and Development, vol. 15, no. 5, pp. 631–639, 2006.
[78]  W. Rust, T. Balakrishnan, and R. Zweigerdt, “Cardiomyocyte enrichment from human embryonic stem cell cultures by selection of ALCAM surface expression,” Regenerative Medicine, vol. 4, no. 2, pp. 225–237, 2009.
[79]  E. Kolossov, Z. Lu, I. Drobinskaya et al., “Identification and characterization of embryonic stem cell-derived pacemaker and atrial cardiomyocytes,” FASEB Journal, vol. 19, no. 6, pp. 577–579, 2005.
[80]  W. C. Claycomb, N. A. Lanson Jr., B. S. Stallworth et al., “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, vol. 95, no. 6, pp. 2979–2984, 1998.
[81]  M. Reppel, F. Pillekamp, K. Brockmeier et al., “The electrocardiogram of human embryonic stem cell-derived cardiomyocytes,” Journal of Electrocardiology, vol. 38, no. 4, pp. 166–170, 2005.
[82]  S. J. Kattman, T. L. Huber, and G. Keller, “Multipotent Flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages,” Developmental Cell, vol. 11, no. 5, pp. 723–732, 2006.
[83]  A. Moretti, L. Caron, A. Nakano et al., “Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification,” Cell, vol. 127, no. 6, pp. 1151–1165, 2006.
[84]  L. Bu, X. Jiang, S. Martin-Puig et al., “Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages,” Nature, vol. 460, no. 7251, pp. 113–117, 2009.
[85]  A. Klaus and W. Birchmeier, “Developmental signaling in myocardial progenitor cells: a comprehensive view of bmp- and wnt/β-catenin signaling,” Pediatric Cardiology, vol. 30, no. 5, pp. 609–616, 2009.
[86]  A. Raya, C. M. Koth, D. Büscher et al., “Activation of Notch signaling pathway precedes heart regeneration in zebrafish,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 1, pp. 11889–11895, 2003.
[87]  M. S. Rones, K. A. McLaughlin, M. Raffin, and M. Mercola, “Serrate and Notch specify cell fates in the heart field by suppressing cardiomyogenesis,” Development, vol. 127, no. 17, pp. 3865–3876, 2000.
[88]  AI. S. Tseng, F. B. Engel, and M. Keating, “The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes,” Chemistry and Biology, vol. 13, no. 9, pp. 957–963, 2006.
[89]  F. B. Engel, M. Schebesta, M. T. Duong et al., “p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes,” Genes and Development, vol. 19, no. 10, pp. 1175–1187, 2005.
[90]  T. C. McDevitt, M. A. Laflamme, and C. E. Murry, “Proliferation of cardiomyocytes derived from human embryonic stem cells is mediated via the IGF/PI 3-kinase/Akt signaling pathway,” Journal of Molecular and Cellular Cardiology, vol. 39, no. 6, pp. 865–873, 2005.
[91]  F. Hattori, H. Chen, H. Yamashita et al., “Nongenetic method for purifying stem cell-derived cardiomyocytes,” Nature Methods, vol. 7, no. 1, pp. 61–66, 2010.
[92]  J. Leschik, S. Stefanovic, B. Brinon, and M. Pucéat, “Cardiac commitment of primate embryonic stem cells,” Nature Protocols, vol. 3, no. 9, pp. 1381–1387, 2008.
[93]  Y. Shiba, K. D. Hauch, and M. A. Laflamme, “Cardiac applications for human pluripotent stem cells,” Current Pharmaceutical Design, vol. 15, no. 24, pp. 2791–2806, 2009.
[94]  D. Anderson, T. Self, I. R. Mellor, G. Goh, S. J. Hill, and C. Denning, “Transgenic enrichment of cardiomyocytes from human embryonic stem cells,” Molecular Therapy, vol. 15, no. 11, pp. 2027–2036, 2007.
[95]  Q. X. Xu, R. Zweigerdt, S. Y. Soo et al., “Highly enriched cardiomyocytes from human embryonic stem cells,” Cytotherapy, vol. 10, no. 4, pp. 376–389, 2008.
[96]  I. Huber, I. Itzhaki, O. Caspi et al., “Identification and selection of cardiomyocytes during human embryonic stem cell differentiation,” FASEB Journal, vol. 21, no. 10, pp. 2551–2563, 2007.
[97]  J. D. Fu, P. Jiang, S. Rushing, J. Liu, N. Chiamvimonvat, and R. A. Li, “Na+/Ca2+ exchanger is a determinant of excitation-contraction coupling in human embryonic stem cell-derived ventricular cardiomyocytes,” Stem Cells and Development, vol. 19, no. 6, pp. 773–782, 2010.
[98]  H. Kita-Matsuo, M. Barcova, N. Prigozhina et al., “Lentiviral vectors and protocols for creation of stable hESC lines for fluorescent tracking and drug resistance selection of cardiomyocytes,” PLoS One, vol. 4, no. 4, Article ID e5046, 2009.
[99]  W.-Z. Zhu, Y. Xie, K. W. Moyes, J. D. Gold, B. Askari, and M. A. Laflamme, “Neuregulin/ErbB signaling regulates cardiac subtype specification in differentiating human embryonic stem cells,” Circulation Research, vol. 107, no. 6, pp. 776–786, 2010.
[100]  C. Kim, M. Majdi, P. Xia et al., “Non-cardiomyocytes influence the electrophysiological maturation of human embryonic stem cell-derived cardiomyocytes during differentiation,” Stem Cells and Development, vol. 19, no. 6, pp. 783–795, 2010.
[101]  M. Snir, I. Kehat, A. Gepstein et al., “Assessment of the ultrastructural and proliferative properties of human embryonic stem cell-derived cardiomyocytes,” American Journal of Physiology, vol. 285, no. 6, pp. H2355–H2363, 2003.
[102]  J. Liu, D. F. Ji, W. S. Chung, and R. A. Li, “Functional sarcoplasmic reticulum for calcium handling of human embryonic stem cell-derived cardiomyocytes: insights for driven maturation,” Stem Cells, vol. 25, no. 12, pp. 3038–3044, 2007.
[103]  A. Norstr?m, K. ?kesson, T. Hardarson, L. Hamberger, P. Bj?rquist, and P. Sartipy, “Molecular and pharmacological properties of human embryonic stem cell-derived cardiomyocytes,” Experimental Biology and Medicine, vol. 231, no. 11, pp. 1753–1762, 2006.
[104]  I. Kehat, A. Gepstein, A. Spira, J. Itskovitz-Eldor, and L. Gepstein, “High-resolution electrophysiological assessment of human embryonic stem cell-derived cardiomyocytes: a novel in vitro model for the study of conduction,” Circulation Research, vol. 91, no. 8, pp. 659–661, 2002.
[105]  L. Sartiani, E. Bettiol, F. Stillitano, A. Mugelli, E. Cerbai, and M. E. Jaconi, “Developmental changes in cardiomyocytes differentiated from human embryonic stem cells: a molecular and electrophysiological approach,” Stem Cells, vol. 25, no. 5, pp. 1136–1144, 2007.
[106]  K. Dolnikov, M. Shilkrut, N. Zeevi-Levin et al., “Functional properties of human embryonic stem cell-derived cardiomyocytes,” Annals of the New York Academy of Sciences, vol. 1047, pp. 66–75, 2005.
[107]  O. Binah, K. Dolnikov, O. Sadan et al., “Functional and developmental properties of human embryonic stem cells-derived cardiomyocytes,” Journal of Electrocardiology, vol. 40, no. 6, pp. S192–S196, 2007.
[108]  M. Brito-Martins, S. E. Harding, and N. N. Ali, “β1- and β2-adrenoceptor responses in cardiomyocytes derived from human embryonic stem cells: comparison with failing and non-failing adult human heart,” British Journal of Pharmacology, vol. 153, no. 4, pp. 751–759, 2008.
[109]  A. Kleger, T. Seufferlein, D. Malan et al., “Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells,” Circulation, vol. 122, no. 18, pp. 1823–1836, 2010.
[110]  M. Ieda, J.-D. Fu, P. Delgado-Olguin et al., “Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors,” Cell, vol. 142, no. 3, pp. 375–386, 2010.

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