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The Current Status of iPS Cells in Cardiac Research and Their Potential for Tissue Engineering and Regenerative Medicine

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Abstract

The recent availability of human cardiomyocytes derived from induced pluripotent stem (iPS) cells opens new opportunities to build in vitro models of cardiac disease, screening for new drugs, and patient-specific cardiac therapy. Notably, the use of iPS cells enables studies in the wide pool of genotypes and phenotypes. We describe progress in reprogramming of induced pluripotent stem (iPS) cells towards the cardiac lineage/differentiation. The focus is on challenges of cardiac disease modeling using iPS cells and their potential to produce safe, effective and affordable therapies/applications with the emphasis of cardiac tissue engineering. We also discuss implications of human iPS cells to biological research and some of the future needs.

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References

  1. Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819), 154–156.

    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(5391), 1145–1147.

    PubMed  CAS  Google Scholar 

  3. Pinto do, O. P., Kolterud, A., & Carlsson, L. (1998). Expression of the LIM-homeobox gene LH2 generates immortalized Steel factor-dependent multipotent hematopoietic precursors. EMBO Journal, 17(19), 5744–5756.

    CAS  Google Scholar 

  4. Shibata, N., Umesono, Y., Orii, H., Sakurai, T., Watanabe, K., & Agata, K. (1999). Expression of vasa(vas)-related genes in germline cells and totipotent somatic stem cells of planarians. Developmental Biology, 206(1), 73–87.

    PubMed  CAS  Google Scholar 

  5. Seydoux, G., & Braun, R. E. (2006). Pathway to totipotency: Lessons from germ cells. Cell, 127(5), 891–904.

    PubMed  CAS  Google Scholar 

  6. Van de Velde, H., Cauffman, G., Tournaye, H., Devroey, P., & Liebaers, I. (2008). The four blastomeres of a 4-cell stage human embryo are able to develop individually into blastocysts with inner cell mass and trophectoderm. Human Reproduction, 23(8), 1742–1747.

    PubMed  Google Scholar 

  7. Yoshida, Y., & Yamanaka, S. (2010). Recent stem cell advances: Induced pluripotent stem cells for disease modeling and stem cell-based regeneration. Circulation, 122(1), 80–87.

    PubMed  Google Scholar 

  8. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–676.

    PubMed  CAS  Google Scholar 

  9. Takahashi, K., Tanabe, K., Ohnuki, M., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861–872.

    PubMed  CAS  Google Scholar 

  10. Yu, J. Y., Vodyanik, M. A., Smuga-Otto, K., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858), 1917–1920.

    PubMed  CAS  Google Scholar 

  11. Robinton, D. A., & Daley, G. Q. (2012). The promise of induced pluripotent stem cells in research and therapy. Nature, 481(7381), 295–305.

    PubMed Central  PubMed  CAS  Google Scholar 

  12. Lowry, W. E., Richter, L., Yachechko, R., et al. (2008). Generation of human induced pluripotent stem cells from dermal fibroblasts. Proceedings of the National Academy of Sciences of the United States of America, 105(8), 2883–2888.

    PubMed Central  PubMed  CAS  Google Scholar 

  13. Huangfu, D. W., Osafune, K., Maehr, R., et al. (2008). Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nature Biotechnology, 26(11), 1269–1275.

    PubMed  CAS  Google Scholar 

  14. Kim, J. B., Zaehres, H., Wu, G. M., et al. (2008). Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature, 454(7204), 646–U54.

    PubMed  CAS  Google Scholar 

  15. Park, I. H., Zhao, R., West, J. A., et al. (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 451(7175), 141–U1.

    PubMed  CAS  Google Scholar 

  16. Loh, Y. H., Hartung, O., Li, H., et al. (2010). Reprogramming of T Cells from human peripheral blood. Cell Stem Cell, 7(1), 15–19.

    PubMed Central  PubMed  Google Scholar 

  17. Aoi, T., Yae, K., Nakagawa, M., et al. (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science, 321(5889), 699–702.

    PubMed  CAS  Google Scholar 

  18. Sugii, S., Kida, Y., Kawamura, T., et al. (2010). Human and mouse adipose-derived cells support feeder-independent induction of pluripotent stem cells. Proceedings of the National Academy of Sciences of the United States of America, 107(8), 3558–3563.

    PubMed Central  PubMed  CAS  Google Scholar 

  19. Maherali, N., Ahfeldt, T., Rigamonti, A., Utikal, J., Cowan, C., & Hochedlinger, K. (2008). A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell, 3(3), 340–345.

    PubMed  CAS  PubMed Central  Google Scholar 

  20. Stadtfeld, M., Maherali, N., Breault, D. T., & Hochedlinger, K. (2008). Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell, 2(3), 230–240.

    PubMed Central  PubMed  CAS  Google Scholar 

  21. Yu, J. Y., Hu, K. J., Smuga-Otto, K., et al. (2009). Human induced pluripotent stem cells free of vector and transgene sequences. Science, 324(5928), 797–801.

    PubMed Central  PubMed  CAS  Google Scholar 

  22. Shao, L. J., Feng, W., Sun, Y., et al. (2009). Generation of iPS cells using defined factors linked via the self-cleaving 2A sequences in a single open reading frame. Cell Research, 19(3), 296–306.

    PubMed Central  PubMed  CAS  Google Scholar 

  23. Sommer, C. A., Stadtfeld, M., Murphy, G. J., Hochedlinger, K., Kotton, D. N., & Mostoslavsky, G. (2009). Induced pluripotent stem cell generation using a single lentiviral stem cell cassette. Stem Cells, 27(3), 543–549.

    PubMed  CAS  Google Scholar 

  24. Anokye-Danso, F., Trivedi, C. M., Juhr, D., et al. (2011). Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell, 8(4), 376–388.

    PubMed Central  PubMed  CAS  Google Scholar 

  25. Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., & Hochedlinger, K. (2008). Induced pluripotent stem cells generated without viral integration. Science, 322(5903), 945–949.

    PubMed  CAS  PubMed Central  Google Scholar 

  26. Zhou, W. B., & Freed, C. R. (2009). Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells, 27(11), 2667–2674.

    PubMed  CAS  Google Scholar 

  27. Okita, K., Nakagawa, M., Hong, H. J., Ichisaka, T., & Yamanaka, S. (2008). Generation of mouse induced pluripotent stem cells without viral vectors. Science, 322(5903), 949–953.

    PubMed  CAS  Google Scholar 

  28. Si-Tayeb, K., Noto, F. K., Sepac, A., et al. (2010). Generation of human induced pluripotent stem cells by simple transient transfection of plasmid DNA encoding reprogramming factors. BMC Developmental Biology, 10.

  29. Kaji, K., Norrby, K., Paca, A., Mileikovsky, M., Mohseni, P., & Woltjen, K. (2009). Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature, 458(7239), 771–U112.

    PubMed Central  PubMed  CAS  Google Scholar 

  30. Woltjen, K., Michael, I. P., Mohseni, P., et al. (2009). piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature, 458(7239), 766–770.

    PubMed Central  PubMed  CAS  Google Scholar 

  31. Belay, E., Matrai, J., Acosta-Sanchez, A., et al. (2010). Novel hyperactive transposons for genetic modification of induced pluripotent and adult stem cells: A nonviral paradigm for coaxed differentiation. Stem Cells, 28(10), 1760–1771.

    PubMed  CAS  Google Scholar 

  32. Kim, D., Kim, C. H., Moon, J. I., et al. (2009). Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell, 4(6), 472–476.

    PubMed Central  PubMed  CAS  Google Scholar 

  33. Zhou, H. Y., Wu, S. L., Joo, J. Y., et al. (2009). Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell, 4(5), 381–384.

    PubMed  CAS  Google Scholar 

  34. Warren, L., Manos, P. D., Ahfeldt, T., et al. (2010). Highly efficient reprogramming to Pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell, 7(5), 618–630.

    PubMed Central  PubMed  CAS  Google Scholar 

  35. Miyoshi, N., Ishii, H., Nagano, H., et al. (2011). Reprogramming of mouse and human cells to pluripotency using mature MicroRNAs. Cell Stem Cell, 8(6), 633–638.

    PubMed  CAS  Google Scholar 

  36. Subramanyam, D., Lamouille, S., Judson, R. L., et al. (2011). Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells. Nature Biotechnology, 29(5), 443–+.

    PubMed Central  PubMed  CAS  Google Scholar 

  37. Sridharan, R., & Plath, K. (2011). Small RNAs loom large during reprogramming. Cell Stem Cell, 8(6), 599–601.

    PubMed Central  PubMed  CAS  Google Scholar 

  38. Fusaki, N., Ban, H., Nishiyama, A., Saeki, K., & Hasegawa, M. (2009). Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proceedings of the Japan Academy Series B-Physical and Biological Sciences, 85(8), 348–362.

    CAS  Google Scholar 

  39. Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448(7151), 313–U1.

    PubMed  CAS  Google Scholar 

  40. Xu, Y., Shi, Y., & Ding, S. (2008). A chemical approach to stem-cell biology and regenerative medicine. Nature, 453(7193), 338–344.

    PubMed  CAS  Google Scholar 

  41. Huangfu, D. W., Maehr, R., Guo, W. J., et al. (2008). Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nature Biotechnology, 26(7), 795–797.

    PubMed  CAS  Google Scholar 

  42. Cho, H. J., Lee, C. S., Kwon, Y. W., et al. (2010). Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation. Blood, 116(3), 386–395.

    PubMed  CAS  Google Scholar 

  43. Shi, Y., Do, J. T., Desponts, C., Hahm, H. S., Scholer, H. R., & Ding, S. (2008). A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell, 2(6), 525–528.

    PubMed  CAS  Google Scholar 

  44. Nakagawa, M., Koyanagi, M., Tanabe, K., et al. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature Biotechnology, 26(1), 101–106.

    PubMed  CAS  Google Scholar 

  45. Wernig, M., Meissner, A., Cassady, J. P., & Jaenisch, R. (2008). c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell, 2(1), 10–12.

    PubMed  CAS  Google Scholar 

  46. Foster, K. W., Liu, Z., Nail, C. D., et al. (2005). Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia. Oncogene, 24(9), 1491–1500.

    PubMed Central  PubMed  CAS  Google Scholar 

  47. Rageul, J., Mottier, S., Jarry, A., et al. (2009). KLF4-dependent, PPARgamma-induced expression of GPA33 in colon cancer cell lines. International Journal of Cancer, 125(12), 2802–2809.

    CAS  Google Scholar 

  48. Martinez-Fernandez, A., Nelson, T. J., Yamada, S., et al. (2009). iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism. Circulation Research, 105(7), 648–656.

    PubMed Central  PubMed  CAS  Google Scholar 

  49. Martinez-Fernandez, A., Nelson, T. J., Ikeda, Y., & Terzic, A. (2010). c-MYC-independent nuclear reprogramming favors cardiogenic potential of induced pluripotent stem cells. Journal of Cardiovascular Translational Research, 3(1), 13–23.

    PubMed Central  PubMed  Google Scholar 

  50. Nakagawa, M., Takizawa, N., Narita, M., Ichisaka, T., & Yamanaka, S. (2010). Promotion of direct reprogramming by transformation-deficient Myc. Proceedings of the National Academy of Sciences of the United States of America, 107(32), 14152–14157.

    PubMed Central  PubMed  CAS  Google Scholar 

  51. Yoshida, Y., Takahashi, K., Okita, K., Ichisaka, T., & Yamanaka, S. (2009). Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell, 5(3), 237–241.

    PubMed  CAS  Google Scholar 

  52. Esteban, M. A., Wang, T., Qin, B. M., et al. (2010). Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell, 6(1), 71–79.

    PubMed  CAS  Google Scholar 

  53. Kim, J. B., Sebastiano, V., Wu, G., et al. (2009). Oct4-induced pluripotency in adult neural stem cells. Cell, 136(3), 411–419.

    PubMed  CAS  Google Scholar 

  54. Marion, R. M., Strati, K., Li, H., et al. (2009). A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature, 460(7259), 1149–U119.

    PubMed Central  PubMed  CAS  Google Scholar 

  55. Kawamura, T., Suzuki, J., Wang, Y. V., et al. (2009). Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature, 460(7259), 1140–U107.

    PubMed Central  PubMed  CAS  Google Scholar 

  56. Hong, H., Takahashi, K., Ichisaka, T., et al. (2009). Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature, 460(7259), 1132–U95.

    PubMed Central  PubMed  CAS  Google Scholar 

  57. Kim, S., Park, C., Han, J. W., et al. (2009). Generation of induced pluripotent stem cells from peripheral blood of coronary artery disease patients. Circulation, 120(18), S1091–S1091.

    Google Scholar 

  58. Kattman, S. J., Witty, A. D., Gagliardi, M., et al. (2011). Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell, 8(2), 228–240.

    PubMed  CAS  Google Scholar 

  59. Meng, X. L., Shen, J. S., Kawagoe, S., Ohashi, T., Brady, R. O., & Eto, Y. (2010). Induced pluripotent stem cells derived from mouse models of lysosomal storage disorders. Proceedings of the National Academy of Sciences of the United States of America, 107(17), 7886–7891.

    PubMed Central  PubMed  CAS  Google Scholar 

  60. Niibe, K., Kawamura, Y., Araki, D., et al. (2011). Purified mesenchymal stem cells are an efficient source for iPS cell induction. Plos One, 6(3).

  61. Sun, N., Panetta, N. J., Gupta, D. M., et al. (2009). Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. Proceedings of the National Academy of Sciences of the United States of America, 106(37), 15720–15725.

    PubMed Central  PubMed  CAS  Google Scholar 

  62. Cai, J., Li, W., Su, H., et al. (2010). Generation of human induced pluripotent stem cells from umbilical cord matrix and amniotic membrane mesenchymal cells. Journal of Biological Chemistry, 285(15), 11227–11234.

    PubMed Central  PubMed  CAS  Google Scholar 

  63. Hanna, J., Markoulaki, S., Schorderet, P., et al. (2008). Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell, 133(2), 250–264.

    PubMed Central  PubMed  CAS  Google Scholar 

  64. Stadtfeld, M., Brennand, K., & Hochedlinger, K. (2008). Reprogramming of pancreatic beta cells into induced pluripotent stem cells. Current Biology, 18(12), 890–894.

    PubMed Central  PubMed  CAS  Google Scholar 

  65. Neubauer, S. (2007). Mechanisms of disease - the failing heart - an engine out of fuel. New England Journal of Medicine, 356(11), 1140–1151.

    PubMed  Google Scholar 

  66. Mancini, D., & Lietz, K. (2010). Selection of cardiac transplantation candidates in 2010. Circulation, 122(2), 173–183.

    PubMed  Google Scholar 

  67. Egashira, T., Yuasa, S., & Fukuda, K. (2011). Induced pluripotent stem cells in cardiovascular medicine. Stem Cells International, 2011(348960).

  68. Narazaki, G., Uosaki, H., Teranishi, M., et al. (2008). Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation, 118(5), 498–506.

    PubMed  Google Scholar 

  69. Burridge, P. W., Keller, G., Gold, J. D., & Wu, J. C. (2012). Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell, 10(1), 16–28.

    PubMed Central  PubMed  CAS  Google Scholar 

  70. 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(21), 2733–2740.

    PubMed  CAS  Google Scholar 

  71. Passier, R., Oostwaard, D. W. V., Snapper, J., et al. (2005). Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures. Stem Cells, 23(6), 772–780.

    PubMed  CAS  Google Scholar 

  72. Freund, C., Oostwaard, D. W. V., Monshouwer-Kloots, J., et al. (2008). Insulin redirects differentiation from cardiogenic mesoderm and endoderm to neuroectoderm in differentiating human embryonic stem cells. Stem Cells, 26(3), 724–733.

    PubMed  CAS  Google Scholar 

  73. Lahti, A. L., Kujala, V. J., Chapman, H., et al. (2012). Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture. Disease Models & Mechanisms, 5(2), 220–230.

    CAS  Google Scholar 

  74. Denning, C., Allegrucci, C., Priddle, H., et al. (2006). Common culture conditions for maintenance and cardiomyocyte differentiation of the human embryonic stem cell lines, BG01 and HUES-7. International Journal of Developmental Biology, 50(1), 27–37.

    PubMed  CAS  Google Scholar 

  75. 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(4), 929–938.

    PubMed  CAS  Google Scholar 

  76. Zhang, J. H., Wilson, G. F., Soerens, A. G., et al. (2009). Functional cardiomyocytes derived from human induced pluripotent stem cells. Circulation Research, 104(4), E30–E41.

    PubMed Central  PubMed  CAS  Google Scholar 

  77. Narsinh, K., Narsinh, K. H., & Wu, J. C. (2011). Derivation of human induced pluripotent stem cells for cardiovascular disease modeling. Circulation Research, 108(9), 1146–1156.

    PubMed  CAS  Google Scholar 

  78. Burridge, P. W., Thompson, S., Millrod, M. A., et al. (2011). A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability. Plos One, 6(4).

  79. Egashira, T., Yuasa, S., Suzuki, T., et al. (2012). Disease characterization using LQTS-specific induced pluripotent stem cells. Cardiovascular Research, 95(4), 419–429.

    PubMed  CAS  Google Scholar 

  80. Bellin, M., Marchetto, M. C., Gage, F. H., & Mummery, C. L. (2012). Induced pluripotent stem cells: the new patient? Nature Reviews Molecular Cell Biology, 13(11), 713–726.

    PubMed  Google Scholar 

  81. 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(9), 1015–1024.

    PubMed  CAS  Google Scholar 

  82. Ojala, M., Rajala, K., Pekkanen-Mattila, M., Miettinen, M., Huhtala, H., & Aalto-Setala, K. (2012). Culture conditions affect cardiac differentiation potential of human pluripotent stem cells. Plos One, 7(10).

  83. Davis, R. P., Casini, S., van den Berg, C. W., et al. (2012). Cardiomyocytes derived from pluripotent stem cells recapitulate electrophysiological characteristics of an overlap syndrome of cardiac sodium channel disease. Circulation, 125(25), 3079–+.

    PubMed  Google Scholar 

  84. Moretti, A., Bellin, M., Welling, A., et al. (2010). Patient-specific induced pluripotent stem-cell models for long-QT syndrome. New England Journal of Medicine, 363(15), 1397–1409.

    PubMed  CAS  Google Scholar 

  85. Ge, X., Ren, Y. M., Bartulos, O., et al. (2012). Modeling supravalvular aortic stenosis syndrome with human induced pluripotent stem cells. Circulation, 126(14), 1695–+.

    PubMed Central  PubMed  Google Scholar 

  86. Sun, N., Yazawa, M., Liu, J. W., et al. (2012). Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy. Science Translational Medicine, 4(130).

  87. Ma, D., Wei, H., Lu, J., et al. (2013) Generation of patient-specific induced pluripotent stem cell-derived cardiomyocytes as a cellular model of arrhythmogenic right ventricular cardiomyopathy. Eur Heart J

  88. 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(3), 407–414.

    PubMed Central  PubMed  CAS  Google Scholar 

  89. Gepstein, L. (2002). Derivation and potential applications of human embryonic stem cells. Circulation Research, 91(10), 866–876.

    PubMed  CAS  Google Scholar 

  90. Xu, C. H., Police, S., Rao, N., & Carpenter, M. K. (2002). Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circulation Research, 91(6), 501–508.

    PubMed  CAS  Google Scholar 

  91. Yang, L., Soonpaa, M. H., Adler, E. D., et al. (2008). Human cardiovascular progenitor cells develop from a KDR plus embryonic-stem-cell-derived population. Nature, 453(7194), 524–U6.

    PubMed  CAS  Google Scholar 

  92. Xu, H. S., Yi, B. A., Wu, H., et al. (2012). Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature. Cell Research, 22(1), 142–154.

    PubMed Central  PubMed  CAS  Google Scholar 

  93. Zwi-Dantsis, L., Huber, I., Habib, M., et al. (2013). Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients. European Heart Journal, 34(21), 1575–1586.

    PubMed  CAS  Google Scholar 

  94. Ng, E. S., Davis, R., Stanley, E. G., & Elefanty, A. G. (2008). A protocol describing the use of a recombinant protein-based, animal product-free medium (APEL) for human embryonic stem cell differentiation as spin embryoid bodies. Nature Protocols, 3(5), 768–776.

    PubMed  CAS  Google Scholar 

  95. Xu, X. Q., Graichen, R., Soo, S. Y., et al. (2008). Chemically defined medium supporting cardiomyocyte differentiation of human embryonic stem cells. Differentiation, 76(9), 958–970.

    PubMed  CAS  Google Scholar 

  96. Uosaki, H., Fukushima, H., Takeuchi, A., et al. (2011). Efficient and scalable purification of cardiomyocytes from human embryonic and induced pluripotent stem cells by VCAM1 surface expression. Plos One, 6(8).

  97. Ban, K., Wile, B., Kim, S., et al. (2013). Purification of cardiomyocytes from differentiating pluripotent stem cells using molecular beacons that target cardiomyocyte-specific mRNA. Circulation, 128(17), 1897–1909.

    PubMed  CAS  Google Scholar 

  98. Hattori, F., Chen, H., Yamashita, H., et al. (2010). Nongenetic method for purifying stem cell-derived cardiomyocytes. Nature Methods, 7(1), 61–U15.

    PubMed  CAS  Google Scholar 

  99. Mauritz, C., Schwanke, K., Reppel, M., et al. (2008). Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation, 118(5), 507–517.

    PubMed  Google Scholar 

  100. Zhang, J. H., Soerens, A. G., Wilson, G. F., Yu, J. Y., Thomson, J. A., & Kamp, T. J. (2009). Human induced pluripotent stem cells free of vector and transgene sequences undergo cardiogenesis in defined conditions. Circulation, 120(18), S1123–S1124.

    Google Scholar 

  101. Germanguz, I., Sedan, O., Zeevi-Levin, N., et al. (2011). Molecular characterization and functional properties of cardiomyocytes derived from human inducible pluripotent stem cells. Journal of Cellular and Molecular Medicine, 15(1), 38–51.

    PubMed  CAS  Google Scholar 

  102. van Laake, L. W., Qian, L., Cheng, P., et al. (2010). Reporter-based isolation of induced pluripotent stem cell- and embryonic stem cell-derived cardiac progenitors reveals limited gene expression variance. Circulation Research, 107(3), 340–347.

    PubMed Central  PubMed  Google Scholar 

  103. Xi, J. Y., Khalil, M., Shishechian, N., et al. (2010). Comparison of contractile behavior of native murine ventricular tissue and cardiomyocytes derived from embryonic or induced pluripotent stem cells. Faseb Journal, 24(8), 2739–2751.

    PubMed  CAS  Google Scholar 

  104. Naito, A. T., Shiojima, I., Akazawa, H., Kikuchi, A., & Komuro, I. (2006). Developmental stage-specific roles of Wnt/ss-catenin signaling in cardiomyogenesis. Circulation, 114(18), 233–233.

    Google Scholar 

  105. Ueno, S., Weidinger, G., Osugi, T., et al. (2007). Biphasic role for Wnt/beta-catenin signaling in cardiac specification in zebrafish and embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 104(23), 9685–9690.

    PubMed Central  PubMed  CAS  Google Scholar 

  106. Klaus, A., Saga, Y., Taketo, M. M., Tzahor, E., & Birchmeier, W. (2007). Distinct roles of Wnt/beta-catenin and Bmp signaling during early cardiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 104(47), 18531–18536.

    PubMed Central  PubMed  CAS  Google Scholar 

  107. Paige, S. L., Osugi, T., Afanasiev, O. K., Pabon, L., Reinecke, H., & Murry, C. E. (2010). Endogenous Wnt/beta-catenin signaling is required for cardiac differentiation in human embryonic stem cells. Plos One, 5(6).

  108. Sa, S., & McCloskey, K. E. (2012). Stage-specific cardiomyocyte differentiation method for H7 and H9 human embryonic stem cells. Stem Cell Reviews and Reports, 8(4), 1120–1128.

    PubMed  CAS  Google Scholar 

  109. Yuasa, S., Itabashi, Y., Koshimizu, U., et al. (2005). Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells. Nature Biotechnology, 23(7), 897–897.

    CAS  Google Scholar 

  110. Cao, N., Liu, Z. M., Chen, Z. Y., et al. (2012). Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells. Cell Research, 22(1), 219–236.

    PubMed Central  PubMed  CAS  Google Scholar 

  111. Fujiwara, M., Yan, P. S., Otsuji, T. G., et al. (2011). Induction and enhancement of cardiac cell differentiation from mouse and human induced pluripotent stem cells with cyclosporin-a. Plos One, 6(2).

  112. Polo, J. M., Liu, S., Figueroa, M. E., et al. (2010). Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nature Biotechnology, 28(8), 848–U130.

    PubMed Central  PubMed  CAS  Google Scholar 

  113. Kim, K., Doi, A., Wen, B., et al. (2010). Epigenetic memory in induced pluripotent stem cells. Nature, 467(7313), 285–U60.

    PubMed Central  PubMed  CAS  Google Scholar 

  114. Hu, Q. R., Friedrich, A. M., Johnson, L. V., & Clegg, D. O. (2010). Memory in induced pluripotent stem cells: reprogrammed human retinal-pigmented epithelial cells show tendency for spontaneous redifferentiation. Stem Cells, 28(11), 1981–1991.

    PubMed  CAS  Google Scholar 

  115. Osafune, K., Caron, L., Borowiak, M., et al. (2008). Marked differences in differentiation propensity among human embryonic stem cell lines. Nature Biotechnology, 26(3), 313–315.

    PubMed  CAS  Google Scholar 

  116. 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(8), 1956–1967.

    PubMed  CAS  Google Scholar 

  117. Davis, R. P., van den Berg, C. W., Casini, S., Braam, S. R., & Mummery, C. L. (2011). Pluripotent stem cell models of cardiac disease and their implication for drug discovery and development. Trends in Molecular Medicine, 17(9), 475–484.

    PubMed  CAS  Google Scholar 

  118. Rosenzweig, A. (2010). Illuminating the potential of pluripotent stem cells. New England Journal of Medicine, 363(15), 1471–1472.

    PubMed  CAS  Google Scholar 

  119. Belmonte, J. C., Ellis, J., Hochedlinger, K., & Yamanaka, S. (2009). Induced pluripotent stem cells and reprogramming: seeing the science through the hype. Nature Reviews Genetics, 10(12), 878–883.

    Google Scholar 

  120. Rolletschek, A., & Wobus, A. M. (2009). Induced human pluripotent stem cells: promises and open questions. Biological Chemistry, 390(9), 845–849.

    PubMed  CAS  Google Scholar 

  121. Pei, D. Q., Xu, J. Y., Zhuang, Q. A., Tse, H. F., & Esteban, M. A. (2010). Induced pluripotent stem cell technology in regenerative medicine and biology. Bioreactor Systems for Tissue Engineering Ii: Strategies for the Expanison and Directed Differentiation of Stem Cells, 123(127–141).

  122. Carvajal-Vergara, X., Sevilla, A., D’Souza, S. L., et al. (2010). Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature, 465(7299), 808–U12.

    PubMed Central  PubMed  CAS  Google Scholar 

  123. Lin, B., Kim, J., Li, Y. X., et al. (2012). High-purity enrichment of functional cardiovascular cells from human iPS cells. Cardiovascular Research, 95(3), 327–335.

    PubMed  CAS  Google Scholar 

  124. Itzhaki, I., Maizels, L., Huber, I., et al. (2011). Modelling the long QT syndrome with induced pluripotent stem cells. Nature, 471(7337), 225–U113.

    PubMed  CAS  Google Scholar 

  125. Matsa, E., Rajamohan, D., Dick, E., et al. (2011). Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation. European Heart Journal, 32(8), 952–962.

    PubMed Central  PubMed  CAS  Google Scholar 

  126. Dirschinger, R. J., Goedel, A., Moretti, A., Laugwitz, K. L., & Sinnecker, D. (2012). Recapitulating long-QT syndrome using induced pluripotent stem cell technology. Pediatric Cardiology, 33(6), 950–958.

    PubMed  Google Scholar 

  127. Yazawa, M., Hsueh, B., Jia, X. L., et al. (2011). Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature, 471(7337), 230–U120.

    PubMed Central  PubMed  CAS  Google Scholar 

  128. Yazawa, M., & Dolmetsch, R. E. (2013). Modeling Timothy syndrome with iPS cells. Journal of Cardiovascular Translational Research, 6(1), 1–9.

    PubMed Central  PubMed  Google Scholar 

  129. Fatima, A., Xu, G. X., Shao, K. F., et al. (2011). In vitro modeling of Ryanodine receptor 2 dysfunction using human induced pluripotent stem cells. Cellular Physiology and Biochemistry, 28(4), 579–592.

    PubMed Central  PubMed  CAS  Google Scholar 

  130. Jung, C. B., Moretti, A., Schnitzler, M. M. Y., et al. (2012). Dantrolene rescues arrhythmogenic RYR2 defect in a patient-specific stem cell model of catecholaminergic polymorphic ventricular tachycardia. EMBO Molecular Medicine, 4(3), 180–191.

    PubMed Central  PubMed  CAS  Google Scholar 

  131. Liu, J., Verma, P. J., Evans-Galea, M. V., et al. (2011). Generation of induced pluripotent stem cell lines from Friedreich Ataxia patients. Stem Cell Reviews and Reports, 7(3), 703–713.

    PubMed  CAS  Google Scholar 

  132. Du, J. T., Campau, E., Soragni, E., et al. (2012). Role of mismatch repair enzymes in GAA.TTC triplet-repeat expansion in Friedreich Ataxia induced pluripotent stem cells. Journal of Biological Chemistry, 287(35), 29861–29872.

    PubMed Central  PubMed  CAS  Google Scholar 

  133. Huang, H. P., Chen, P. H., Hwu, W. L., et al. (2011). Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification. Human Molecular Genetics, 20(24), 4851–4864.

    PubMed  CAS  Google Scholar 

  134. Huang, H. P., Chuang, C. Y., & Kuo, H. C. (2012). Induced pluripotent stem cell technology for disease modeling and drug screening with emphasis on lysosomal storage diseases. Stem Cell Research & Therapy, 3.

  135. Clegg, S., Gong, Q., Zhou, Z. and Adler, E (2011) A novel in vitro model of Danon disease confirms the critical role of LAMP2 in regulating autophagy. In AHA/ASA.

  136. Kamp, T. J., & Lyons, G. E. (2009). On the road to iPS cell cardiovascular applications. Circulation Research, 105(7), 617–619.

    PubMed Central  PubMed  CAS  Google Scholar 

  137. Saha, K., & Jaenisch, R. (2009). Technical challenges in using human induced pluripotent stem cells to model disease. Cell Stem Cell, 5(6), 584–595.

    PubMed Central  PubMed  CAS  Google Scholar 

  138. Yoshida, Y., & Yamanaka, S. (2011). iPS cells: A source of cardiac regeneration. Journal of Molecular and Cellular Cardiology, 50(2), 327–332.

    PubMed  CAS  Google Scholar 

  139. Park, I. H., Arora, N., Huo, H., et al. (2008). Disease-specific induced pluripotent stem cells. Cell, 134(5), 877–886.

    PubMed Central  PubMed  CAS  Google Scholar 

  140. Sarkozy, A., Digilio, M. C., & Dallapiccola, B. (2008). Leopard syndrome. Orphanet Journal of Rare Diseases, 3(13).

  141. Marban, E. (2002). Cardiac channelopathies. Nature, 415(6868), 213–218.

    PubMed  CAS  Google Scholar 

  142. Sanguinetti, M. C., & Tristani-Firouzi, M. (2006). hERG potassium channels and cardiac arrhythmia. Nature, 440(7083), 463–469.

    PubMed  CAS  Google Scholar 

  143. Goldenberg, I., & Moss, A. J. (2008). Long QT syndrome. Journal of the American College of Cardiology, 51(24), 2291–2300.

    PubMed  Google Scholar 

  144. Wilde, A. A. M., & Bezzina, C. R. (2005). Genetics of cardiac arrhythmias. Heart, 91(10), 1352–1358.

    PubMed Central  PubMed  CAS  Google Scholar 

  145. Splawski, I., Timothy, K. W., Sharpe, L. M., et al. (2004). Ca(v)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell, 119(1), 19–31.

    PubMed  CAS  Google Scholar 

  146. Priori, S. G., Napolitano, C., Memmi, M., et al. (2002). Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation, 106(1), 69–74.

    PubMed  CAS  Google Scholar 

  147. Scheinman, M. M., & Lam, J. (2006). Exercise-induced ventricular arrhythmias in patients with no structural cardiac disease. Annual Review of Medicine, 57(473–484).

    Google Scholar 

  148. Basso, C., Corrado, D., Marcus, F. I., Nava, A., & Thiene, G. (2009). Arrhythmogenic right ventricular cardiomyopathy. Lancet, 373(9671), 1289–1300.

    PubMed  Google Scholar 

  149. Arad, M., Maron, B. J., Gorham, J. M., et al. (2005). Glycogen storage diseases presenting as hypertrophic cardiomyopathy. New England Journal of Medicine, 352(4), 362–372.

    PubMed  CAS  Google Scholar 

  150. Vunjak-Novakovic, G. (2008). Patterning stem cell differentiation. Cell Stem Cell, 3(4), 362–363.

    PubMed Central  PubMed  CAS  Google Scholar 

  151. Stamm, C., Klose, K., & Choi, Y. H. (2010). Clinical application of stem cells in the cardiovascular system. Bioreactor Systems for Tissue Engineering Ii: Strategies for the Expanison and Directed Differentiation of Stem Cells, 123(293–317).

  152. Soonpaa, M. H., Koh, G. Y., Klug, M. G., & Field, L. J. (1994). Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium. Science, 264(5155), 98–101.

    PubMed  CAS  Google Scholar 

  153. Orlic, D., Kajstura, J., Chimenti, S., et al. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410(6829), 701–705.

    PubMed  CAS  Google Scholar 

  154. Zhang, M., Methot, D., Poppa, V., Fujio, Y., Walsh, K., & Murry, C. E. (2001). Cardiomyocyte grafting for cardiac repair: Graft cell death and anti-death strategies. Journal of Molecular and Cellular Cardiology, 33(5), 907–921.

    PubMed  CAS  Google Scholar 

  155. Dow, J., Simkhovich, B. Z., Kedes, L., & Kloner, R. A. (2005). Washout of transplanted cells from the heart: A potential new hurdle for cell transplantation therapy. Cardiovascular Research, 67(2), 301–307.

    PubMed  CAS  Google Scholar 

  156. Qiao, H., Surti, S., Choi, S. R., et al. (2009). Death and proliferation time course of stem cells transplanted in the myocardium. Molecular Imaging and Biology, 11(6), 408–414.

    PubMed Central  PubMed  Google Scholar 

  157. Hofmann, M., Wollert, K. C., Meyer, G. P., et al. (2005). Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation, 111(17), 2198–2202.

    PubMed  Google Scholar 

  158. Vunjak-Novakovic, G., Tandon, N., Godier, A., et al. (2010). Challenges in cardiac tissue engineering. Tissue Engineering. Part B, Reviews, 16(2), 169–187.

    PubMed Central  PubMed  Google Scholar 

  159. Jawad, H., Ali, N. N., Lyon, A. R., Chen, Q. Z., Harding, S. E., & Boccaccini, A. R. (2007). Myocardial tissue engineering: a review. Journal of Tissue Engineering and Regenerative Medicine, 1(5), 327–342.

    PubMed  CAS  Google Scholar 

  160. Zimmermann, W. H. (2008). Tissue engineering polymers flex their muscles. Nature Materials, 7(12), 932–933.

    PubMed  CAS  Google Scholar 

  161. Rosellini, E., Cristallini, C., Barbani, N., Vozzi, G., & Giusti, P. (2009). Preparation and characterization of alginate/gelatin blend films for cardiac tissue engineering. Journal of Biomedical Materials Research, Part A, 91A(2), 447–453.

    CAS  Google Scholar 

  162. Zhang, T., Wan, L. Q., Xiong, Z., et al. (2012). Channelled scaffolds for engineering myocardium with mechanical stimulation. Journal of Tissue Engineering and Regenerative Medicine, 6(9), 748–756.

    CAS  Google Scholar 

  163. Chimenti, I., Rizzitelli, G., Gaetani, R., et al. (2011). Human cardiosphere-seeded gelatin and collagen scaffolds as cardiogenic engineered bioconstructs. Biomaterials, 32(35), 9271–9281.

    PubMed  CAS  Google Scholar 

  164. Tandon, N., Marsano, A., Maidhof, R., Wan, L., Park, H., & Vunjak-Novakovic, G. (2011). Optimization of electrical stimulation parameters for cardiac tissue engineering. Journal of Tissue Engineering and Regenerative Medicine, 5(6), E115–E125.

    PubMed Central  PubMed  CAS  Google Scholar 

  165. Chi, N. H., Yang, M. C., Chung, T. W., Chen, J. Y., Chou, N. K., & Wang, S. S. (2012). Cardiac repair achieved by bone marrow mesenchymal stem cells/silk fibroin/hyaluronic acid patches in a rat of myocardial infarction model. Biomaterials, 33(22), 5541–5551.

    PubMed  CAS  Google Scholar 

  166. Patra, C., Talukdar, S., Novoyatleva, T., et al. (2012). Silk protein fibroin from Antheraea mylitta for cardiac tissue engineering. Biomaterials, 33(9), 2673–2680.

    PubMed  CAS  Google Scholar 

  167. Godier-Furnemont, A. F. G., Martens, T. P., Koeckert, M. S., et al. (2011). Composite scaffold provides a cell delivery platform for cardiovascular repair. Proceedings of the National Academy of Sciences of the United States of America, 108(19), 7974–7979.

    PubMed Central  PubMed  CAS  Google Scholar 

  168. Marsano, A., Maidhof, R., Luo, J. W., et al. (2013). The effect of controlled expression of VEGF by transduced myoblasts in a cardiac patch on vascularization in a mouse model of myocardial infarction. Biomaterials, 34(2), 393–401.

    PubMed Central  PubMed  CAS  Google Scholar 

  169. Kuo, Y. C., & Huang, M. J. (2012). Material-driven differentiation of induced pluripotent stem cells in neuron growth factor-grafted poly(epsilon-caprolactone)-poly(beta-hydroxybutyrate) scaffolds. Biomaterials, 33(23), 5672–5682.

    PubMed  CAS  Google Scholar 

  170. Wen, Y., Wang, F., Zhang, W. C., et al. (2012). Application of induced pluripotent stem cells in generation of a tissue-engineered tooth-like structure. Tissue Engineering Part A, 18(15–16), 1677–1685.

    PubMed Central  PubMed  CAS  Google Scholar 

  171. Miki, K., Uenaka, H., Saito, A., et al. (2012). Bioengineered myocardium derived from induced pluripotent stem cells improves cardiac function and attenuates cardiac remodeling following chronic myocardial infarction in rats. Stem Cells Translational Medicine, 1(5), 430–437.

    PubMed Central  PubMed  CAS  Google Scholar 

  172. 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(5), 408–416.

    PubMed Central  PubMed  Google Scholar 

  173. Mauritz, C., Martens, A., Rojas, S. V., et al. (2011). Induced pluripotent stem cell (iPSC)-derived Flk-1 progenitor cells engraft, differentiate, and improve heart function in a mouse model of acute myocardial infarction. European Heart Journal, 32(21), 2634–2641.

    PubMed  CAS  Google Scholar 

  174. Okano, T., Yamada, N., Okuhara, M., Sakai, H., & Sakurai, Y. (1995). Mechanism of cell detachment from temperature-modulated, hydrophilic-hydrophobic polymer surfaces. Biomaterials, 16(4), 297–303.

    PubMed  CAS  Google Scholar 

  175. Miki, K., Saito, A., Uenaka, H., et al. (2009). Cardiomyocyte sheets derived from induced pluripotent stem (iPS) cells improve cardiac function and attenuate cardiac remodeling in myocardial infarction in mice. Circulation, 120(18), S721–S721.

    Google Scholar 

  176. Haraguchi, Y., Matsuura, K., Shimizu, T., Yamato, M., & Okano, T. (2012). Expansion and cardiac differentiation of human iPS cells using a suspension culture system. Journal of Tissue Engineering and Regenerative Medicine, 6(252–252).

    Google Scholar 

  177. Matsuura, K. M., Shimizu, T. S., Wada, M. W., et al. (2012). Creation of cell sheet-based bioengineered heart tissue using ES/iPS cells-derived cells. Journal of Tissue Engineering and Regenerative Medicine, 6(103–103).

    Google Scholar 

  178. Sawa, Y., Miyagawa, S., Sakaguchi, T., et al. (2012). Tissue engineered myoblast sheets improved cardiac function sufficiently to discontinue LVAS in a patient with DCM: report of a case. Surgery Today, 42(2), 181–184.

    PubMed  Google Scholar 

  179. Hibino, N., Duncan, D. R., Nalbandian, A., et al. (2012). Evaluation of the use of an induced puripotent stem cell sheet for the construction of tissue-engineered vascular grafts. Journal of Thoracic and Cardiovascular Surgery, 143(3), 696–703.

    PubMed Central  PubMed  CAS  Google Scholar 

  180. Tulloch, N. L., Muskheli, V., Razumova, M. V., et al. (2011). Growth of engineered human myocardium with mechanical loading and vascular coculture. Circulation Research, 109(1), 47–U195.

    PubMed Central  PubMed  CAS  Google Scholar 

  181. Eschenhagen, T., Fink, C., Remmers, U., et al. (1997). Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system. Faseb Journal, 11(8), 683–694.

    PubMed  CAS  Google Scholar 

  182. Zimmermann, W. H., Fink, C., Kralisch, D., Remmers, U., Weil, J., & Eschenhagen, T. (2000). Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes. Biotechnology and Bioengineering, 68(1), 106–114.

    PubMed  CAS  Google Scholar 

  183. Eschenhagen, T. (2011). The beat goes on: human heart muscle from pluripotent stem cells. Circulation Research, 109(1), 1–3.

    Google Scholar 

  184. Miura, K., Okada, Y., Aoi, T., et al. (2009). Variation in the safety of induced pluripotent stem cell lines. Nature Biotechnology, 27(8), 743–745.

    PubMed  CAS  Google Scholar 

  185. Yamanaka, S. (2010). Patient-specific pluripotent stem cells become even more accessible. Cell Stem Cell, 7(1), 1–2.

    PubMed  CAS  Google Scholar 

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Acknowledgments

AMM acknowledges “Fundação para a Ciência e Tecnologia” (FCT) for the Postdoctoral grant (SFRH/BPD/66897/2009) financed by POPH - QREN – Advanced Formation, and co-financed by Social European Fund and National Fund from MCTES. GVN acknowledges funding by NIH (grants HL076485, EB 17103, EB 002520 and HL108668) and NYSTEM (grant C026449).

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Martins, A.M., Vunjak-Novakovic, G. & Reis, R.L. The Current Status of iPS Cells in Cardiac Research and Their Potential for Tissue Engineering and Regenerative Medicine. Stem Cell Rev and Rep 10, 177–190 (2014). https://doi.org/10.1007/s12015-013-9487-7

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