Murry, C.E., Reinecke, H. & Pabon, L.M. Regeneration gaps: observations on stem cells and cardiac repair. J. Am. Coll. Cardiol. 47, 1777–1785 (2006).
Go, A.S. et al. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation 127, e6–e245 (2013).
Chugh, A.R. et al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation 126, S54–S64 (2012).
Bolli, R. et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 378, 1847–1857 (2011).
Makkar, R.R. et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 379, 895–904 (2012).
Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).
Doetschman, T.C., Eistetter, H., Katz, M., Schmidt, W. & Kemler, R. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J. Embryol. Exp. Morphol. 87, 27–45 (1985).
Kattman, S.J. et al. Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8, 228–240 (2011).
Willems, E. et al. Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell–derived mesoderm. Circ. Res. 109, 360–364 (2011).
Burridge, P.W. et al. A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability. PLoS ONE 6, e18293 (2011).
Elliott, D.A. et al. NKX2-5(eGFP/w) hESCs for isolation of human cardiac progenitors and cardiomyocytes. Nat. Methods 8, 1037–1040 (2011).
Zhang, Q. et al. Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals. Cell Res. 21, 579–587 (2011).
Uosaki, H. et al. Efficient and scalable purification of cardiomyocytes from human embryonic and induced pluripotent stem cells by VCAM1 surface expression. PLoS ONE 6, e23657 (2011).
Hudson, J., Titmarsh, D., Hidalgo, A., Wolvetang, E. & Cooper-White, J. Primitive cardiac cells from human embryonic stem cells. Stem Cells Dev. 21, 1513–1523 (2012).
Burridge, P.W., Keller, G., Gold, J.D. & Wu, J.C. Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10, 16–28 (2012).
Dubois, N.C. et al. SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells. Nat. Biotechnol. 29, 1011–1018 (2011).
Tohyama, S. et al. Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell–derived cardiomyocytes. Cell Stem Cell 12, 127–137 (2013).
Shiba, Y. et al. Human ES-cell–derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. Nature 489, 322–325 (2012).
Segers, V.F. & Lee, R.T. Biomaterials to enhance stem cell function in the heart. Circ. Res. 109, 910–922 (2011).
Vunjak-Novakovic, G., Lui, K.O., Tandon, N. & Chien, K.R. Bioengineering heart muscle: a paradigm for regenerative medicine. Annu. Rev. Biomed. Eng. 13, 245–267 (2011).
Masuda, S., Shimizu, T., Yamato, M. & Okano, T. Cell sheet engineering for heart tissue repair. Adv. Drug Deliv. Rev. 60, 277–285 (2008).
Li, R.K. et al. Survival and function of bioengineered cardiac grafts. Circulation 100, II63–II69 (1999).
Kofidis, T. et al. Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle. J. Thorac. Cardiovasc. Surg. 128, 571–578 (2004).
Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).
Staerk, J. et al. Reprogramming of human peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell 7, 20–24 (2010).
Loh, Y.H. et al. Reprogramming of T cells from human peripheral blood. Cell Stem Cell 7, 15–19 (2010).
Seki, T. et al. Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell 7, 11–14 (2010).
Zhou, T. et al. Generation of induced pluripotent stem cells from urine. J. Am. Soc. Nephrol. 22, 1221–1228 (2011).
Reiter, J.F. et al. Gata5 is required for the development of the heart and endoderm in zebrafish. Genes Dev. 13, 2983–2995 (1999).
Latinkić, B.V., Kotecha, S. & Mohun, T.J. Induction of cardiomyocytes by GATA4 in Xenopus ectodermal explants. Development 130, 3865–3876 (2003).
David, R. et al. MesP1 drives vertebrate cardiovascular differentiation through Dkk-1–mediated blockade of Wnt-signalling. Nat. Cell Biol. 10, 338–345 (2008).
Bondue, A. et al. Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification. Cell Stem Cell 3, 69–84 (2008).
Lindsley, R.C. et al. Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs. Cell Stem Cell 3, 55–68 (2008).
Takeuchi, J.K. & Bruneau, B.G. Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 459, 708–711 (2009).
Davis, R.L., Weintraub, H. & Lassar, A.B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987–1000 (1987).
Wang, Z., Wang, D.Z., Pipes, G.C. & Olson, E.N. Myocardin is a master regulator of smooth muscle gene expression. Proc. Natl. Acad. Sci. USA 100, 7129–7134 (2003).
Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J. & Melton, D.A. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455, 627–632 (2008).
Feng, R. et al. PU.1 and C/EBPα/β convert fibroblasts into macrophage-like cells. Proc. Natl. Acad. Sci. USA 105, 6057–6062 (2008).
Vierbuchen, T. et al. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463, 1035–1041 (2010).
Addis, R.C. et al. Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector. PLoS ONE 6, e28719 (2011).
Caiazzo, M. et al. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 476, 224–227 (2011).
Kim, J. et al. Direct reprogramming of mouse fibroblasts to neural progenitors. Proc. Natl. Acad. Sci. USA 108, 7838–7843 (2011).
Huang, P. et al. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475, 386–389 (2011).
Sekiya, S. & Suzuki, A. Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature 475, 390–393 (2011).
Kelly, M.C., Chang, Q., Pan, A., Lin, X. & Chen, P. Atoh1 directs the formation of sensory mosaics and induces cell proliferation in the postnatal mammalian cochlea in vivo. J. Neurosci. 32, 6699–6710 (2012).
Liu, Z. et al. Age-dependent in vivo conversion of mouse cochlear pillar and Deiters' cells to immature hair cells by Atoh1 ectopic expression. J. Neurosci. 32, 6600–6610 (2012).
Buganim, Y. et al. Direct reprogramming of fibroblasts into embryonic sertoli-like cells by defined factors. Cell Stem Cell 11, 373–386 (2012).
Blau, H.M. et al. Plasticity of the differentiated state. Science 230, 758–766 (1985).
Evans, S.M., Tai, L.J., Tan, V.P., Newton, C.B. & Chien, K.R. Heterokaryons of cardiac myocytes and fibroblasts reveal the lack of dominance of the cardiac muscle phenotype. Mol. Cell. Biol. 14, 4269–4279 (1994).
Ieda, M. et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142, 375–386 (2010).
Chen, J.X. et al. Inefficient reprogramming of fibroblasts into cardiomyocytes using gata4, mef2c, and tbx5. Circ. Res. 111, 50–55 (2012).
Srivastava, D. & Ieda, M. Critical factors for cardiac reprogramming. Circ. Res. 111, 5–8 (2012).
Inagawa, K. & Ieda, M. Direct reprogramming of mouse fibroblasts into cardiac myocytes. J. Cardiovasc. Transl. Res. 6, 37–45 (2013).
Wang, B. et al. Reprogramming efficiency and quality of induced pluripotent stem cells (iPSCs) generated from muscle-derived fibroblasts of mdx mice at different ages. PLoS Curr. 3, RRN1274 (2011).
Song, K. et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature 485, 599–604 (2012).
Protze, S. et al. A new approach to transcription factor screening for reprogramming of fibroblasts to cardiomyocyte-like cells. J. Mol. Cell. Cardiol. 53, 323–332 (2012).
Jayawardena, T.M. et al. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ. Res. 110, 1465–1473 (2012).
Anokye-Danso, F. et al. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 8, 376–388 (2011).
Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 (2007).
Kim, J. et al. Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. Cell Stem Cell 9, 413–419 (2011).
Pfisterer, U. et al. Direct conversion of human fibroblasts to dopaminergic neurons. Proc. Natl. Acad. Sci. USA 108, 10343–10348 (2011).
He, J.Q., Ma, Y., Lee, Y., Thomson, J.A. & Kamp, T.J. Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ. Res. 93, 32–39 (2003).
Otsuji, T.G. et al. Progressive maturation in contracting cardiomyocytes derived from human embryonic stem cells: qualitative effects on electrophysiological responses to drugs. Stem Cell Res. 4, 201–213 (2010).
Qian, L. et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 485, 593–598 (2012).
Inagawa, K. et al. Induction of cardiomyocyte-like cells in infarct hearts by gene transfer of gata4, mef2c, and tbx5. Circ. Res. 111, 1147–1156 (2012).
Mathison, M. et al. In vivo cardiac cellular reprogramming efficacy is enhanced by angiogenic preconditioning of the infarcted myocardium with vascular endothelial growth factor. J. Am. Heart. Assoc. 1, e005652 (2012).
Kim, T.K. et al. Transcriptome transfer provides a model for understanding the phenotype of cardiomyocytes. Proc. Natl. Acad. Sci. USA 108, 11918–11923 (2011).
Mummery, C.L. et al. Differentiation of human embryonic stem cells and induced pluripotent stem cells to cardiomyocytes: a methods overview. Circ. Res. 111, 344–358 (2012).
Addis, R.C. et al. Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success. J. Mol. Cell. Cardiol. 60, 97–106 (2013).
DeHaan, R.L. & Gottlieb, S.H. The electrical activity of embryonic chick heart cells isolated in tissue culture singly or in interconnected cell sheets. J. Gen. Physiol. 52, 643–665 (1968).
Davies, M.P. et al. Developmental changes in ionic channel activity in the embryonic murine heart. Circ. Res. 78, 15–25 (1996).
Satin, J. et al. Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes. J. Physiol. (Lond.) 559, 479–496 (2004).
Islas, J.F. et al. Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors. Proc. Natl. Acad. Sci. USA 109, 13016–13021 (2012).
Nam, Y.J. et al. Reprogramming of human fibroblasts toward a cardiac fate. Proc. Natl. Acad. Sci. USA 110, 5588–5593 (2013).
Chiu, L.L., Iyer, R.K., Reis, L.A., Nunes, S.S. & Radisic, M. Cardiac tissue engineering: current state and perspectives. Front. Biosci. 17, 1533–1550 (2012).
Boudou, T. et al. A microfabricated platform to measure and manipulate the mechanics of engineered cardiac microtissues. Tissue Eng. Part A 18, 910–919 (2012).
Efe, J.A. et al. Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat. Cell Biol. 13, 215–222 (2011).
Christoforou, N. et al. Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming. PLoS One 8, e63577 (2013).
Bers, D.M. Cardiac excitation-contraction coupling. Nature 415, 198–205 (2002).
Tian, L. et al. Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nat. Methods 6, 875–881 (2009).
Tallini, Y.N. et al. Imaging cellular signals in the heart in vivo: cardiac expression of the high-signal Ca2+ indicator GCaMP2. Proc. Natl. Acad. Sci. USA 103, 4753–4758 (2006).