Abstract
Myocardial stem cell therapies are emerging as novel therapeutic paradigms for myocardial repair, but are hampered by the lack of sources for autologous human cardiomyocytes. An exciting development in the field of cardiovascular regenerative medicine is the ability to reprogram adult somatic cells into pluripotent stem cell lines (induced pluripotent stem cells, iPSCs) and to coax their differentiation into functional cardiomyocytes. This technology holds great promise for the emerging disciplines of personalized and regenerative medicine, because of the ability to derive patient-specific iPSCs that could potentially elude the immune system. The current review describes the latest techniques of generating iPSCs as well as the methods used to direct their differentiation towards the cardiac lineage. We then detail the unique potential as well as the possible hurdles on the road to clinical utilizing of the iPSCs derived cardiomyocytes in the emerging field of cardiovascular regenerative medicine.
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Abbreviations
- CPCs:
-
Cardiac progenitor cells
- EBs:
-
Embryoid bodies
- ESCs:
-
Embryonic stem cells
- hESCs:
-
Human embryonic stem cells
- hiPSCs:
-
Human-induced pluripotent stem cells
- hiPSCs-CMs:
-
Human-induced pluripotent stem cells-derived cardiomyocytes
- hPSCs:
-
Human pluripotent stem cells
- iPSCs:
-
Induced pluripotent stem cells
- miPSCs:
-
Murine-induced pluripotent stem cells
- miRNAs:
-
MicroRNAs
- MSCs:
-
Mesenchymal stem cells
References
Cohn JN, Bristow MR, Chien KR, Colucci WS, Frazier OH et al (1997) Report of the National Heart, Lung, and Blood Institute Special Emphasis Panel on Heart Failure Research. Circulation 95:766–770
Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102
Kajstura J, Gurusamy N, Ogorek B, Goichberg P, Clavo-Rondon C et al (2010) Myocyte turnover in the aging human heart. Circ Res 107:1374–1386
Parmacek MS, Epstein JA (2009) Cardiomyocyte renewal. N Engl J Med 361:86–88
Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA et al (2011) Transient regenerative potential of the neonatal mouse heart. Science 331:1078–1080
Leri A, Kajstura J, Anversa P (2011) Role of cardiac stem cells in cardiac pathophysiology: a paradigm shift in human myocardial biology. Circ Res 109:941–961
Dimmeler S, Zeiher AM, Schneider MD (2005) Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 115:572–583
Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23:845–856
Passier R, van Laake LW, Mummery CL (2008) Stem-cell-based therapy and lessons from the heart. Nature 453:322–329
Segers VF, Lee RT (2008) Stem-cell therapy for cardiac disease. Nature 451:937–942
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872
Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920
Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F et al (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776
Messina E, De Angelis L, Frati G, Morrone S, Chimenti S et al (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95:911–921
Barile L, Messina E, Giacomello A, Marban E (2007) Endogenous cardiac stem cells. Prog Cardiovasc Dis 50:31–48
Mohsin S, Siddiqi S, Collins B, Sussman MA (2011) Empowering adult stem cells for myocardial regeneration. Circ Res 109:1415–1428
Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156
Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78:7634–7638
Levenberg S, Golub JS, Amit M, Itskovitz-Eldor J, Langer R (2002) Endothelial cells derived from human embryonic stem cells. Proc Natl Acad Sci USA 99:4391–4396
Dar A, Domev H, Ben-Yosef O, Tzukerman M, Zeevi-Levin N et al (2012) Multipotent vasculogenic pericytes from human pluripotent stem cells promote recovery of murine ischemic limb. Circulation 125:87–99
He JQ, Ma Y, Lee Y, Thomson JA, Kamp TJ (2003) Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ Res 93:32–39
Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M et al (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 108:407–414
Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA et al (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25:1015–1024
Mummery C, Ward-van Oostwaard D, Doevendans P, Spijker R, van den Brink S et al (2003) Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. Circulation 107:2733–2740
Tomescot A, Leschik J, Bellamy V, Dubois G, Messas E et al (2007) Differentiation in vivo of cardiac committed human embryonic stem cells in postmyocardial infarcted rats. Stem Cells 25:2200–2205
Xu C, Police S, Rao N, Carpenter MK (2002) Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res 91:501–508
Yang L, Soonpaa MH, Adler ED, Roepke TK, Kattman SJ et al (2008) Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature 453:524–528
Caspi O, Itzhaki I, Kehat I, Gepstein A, Arbel G et al (2009) In vitro electrophysiological drug testing using human embryonic stem cell derived cardiomyocytes. Stem Cells Dev 18:161–172
Dick E, Rajamohan D, Ronksley J, Denning C (2010) Evaluating the utility of cardiomyocytes from human pluripotent stem cells for drug screening. Biochem Soc Trans 38:1037–1045
Gepstein L (2002) Derivation and potential applications of human embryonic stem cells. Circ Res 91:866–876
Kehat I, Gepstein L (2003) Human embryonic stem cells for myocardial regeneration. Heart Fail Rev 8:229–236
Shiba Y, Hauch KD, Laflamme MA (2009) Cardiac applications for human pluripotent stem cells. Curr Pharm Des 15:2791–2806
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676
Haase A, Olmer R, Schwanke K, Wunderlich S, Merkert S et al (2009) Generation of induced pluripotent stem cells from human cord blood. Cell Stem Cell 5:434–441
Zhang J, Wilson GF, Soerens AG, Koonce CH, Yu J et al (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res 104:e30–e41
Zwi L, Caspi O, Arbel G, Huber I, Gepstein A et al (2009) Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation 120:1513–1523
Carvajal-Vergara X, Sevilla A, D’Souza SL, Ang YS, Schaniel C et al (2010) Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 465:808–812
Itzhaki I, Maizels L, Huber I, Zwi-Dantsis L, Caspi O et al (2011) Modelling the long QT syndrome with induced pluripotent stem cells. Nature 471:225–229
Moretti A, Bellin M, Welling A, Jung CB, Lam JT et al (2010) Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med 363:1397–1409
Amabile G, Meissner A (2009) Induced pluripotent stem cells: current progress and potential for regenerative medicine. Trends Mol Med 15:59–68
Hanna J, Saha K, Pando B, van Zon J, Lengner CJ et al (2009) Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462:595–601
Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A et al (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26:1276–1284
Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K et al (2008) Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321:699–702
Hanna J, Markoulaki S, Schorderet P, Carey BW, Beard C et al (2008) Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133:250–264
Robinton DA, Daley GQ (2012) The promise of induced pluripotent stem cells in research and therapy. Nature 481:295–305
Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW et al (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136:964–977
Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M et al (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458:766–770
Yusa K, Rad R, Takeda J, Bradley A (2009) Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon. Nat Methods 6:363–369
Kim D, Kim CH, Moon JI, Chung YG, Chang MY et al (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476
Zhou H, Wu S, Joo JY, Zhu S, Han DW et al (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4:381–384
Warren L, Manos PD, Ahfeldt T, Loh YH, Li H et al (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7:618–630
Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M et al (2008) Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26:795–797
Ichida JK, Blanchard J, Lam K, Son EY, Chung JE et al (2009) A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell 5:491–503
Mauritz C, Schwanke K, Reppel M, Neef S, Katsirntaki K et al (2008) Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation 118:507–517
Narazaki G, Uosaki H, Teranishi M, Okita K, Kim B et al (2008) Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation 118:498–506
Zwi-Dantsis L, Mizrahi I, Arbel G, Gepstein A, Gepstein L (2011) Scalable Production of Cardiomyocytes Derived from c-Myc Free Induced Pluripotent Stem Cells. Tissue Eng Part A 17:1027–1037
Martinez-Fernandez A, Nelson TJ, Yamada S, Reyes S, Alekseev AE et al (2009) iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism. Circ Res 105:648–656
Martinez-Fernandez A, Nelson TJ, Ikeda Y, Terzic A (2010) c-MYC independent nuclear reprogramming favors cardiogenic potential of induced pluripotent stem cells. J Cardiovasc Transl Res 3:13–23
Ma J, Guo L, Fiene SJ, Anson BD, Thomson JA et al (2011) High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents. Am J Physiol Heart Circ Physiol 301:H2006–H2017
Itzhaki I, Rapoport S, Huber I, Mizrahi I, Zwi-Dantsis L et al (2011) Calcium handling in human induced pluripotent stem cell derived cardiomyocytes. PLoS One 6:e18037
Zwi-Dantsis L, Huber I, Habib M, Winterstern A, Gepstein A, et al. (2012) Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients. Eur Heart J (in press)
Lev S, Kehat I, Gepstein L (2005) Differentiation pathways in human embryonic stem cell-derived cardiomyocytes. Ann NY Acad Sci 1047:50–65
Burridge PW, Keller G, Gold JD, Wu JC (2012) Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10:16–28
Murry CE, Keller G (2008) Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell 132:661–680
Passier R, Oostwaard DW, Snapper J, Kloots J, Hassink RJ et al (2005) Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures. Stem Cells 23:772–780
Graichen R, Xu X, Braam SR, Balakrishnan T, Norfiza S et al (2008) Enhanced cardiomyogenesis of human embryonic stem cells by a small molecular inhibitor of p38 MAPK. Differentiation 76:357–370
Kattman SJ, Witty AD, Gagliardi M, Dubois NC, Niapour 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 8:228–240
Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y et al (2010) Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142:375–386
Efe JA, Hilcove S, Kim J, Zhou H, Ouyang K et al (2011) Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat Cell Biol 13:215–222
Qian L, Huang Y, Spencer CI, Foley A, Vedantham V et al (2012) In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 485:593–598
Song K, Nam YJ, Luo X, Qi X, Tan W et al (2012) Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature 485:599–604
Caspi O, Huber I, Kehat I, Habib M, Arbel G et al (2007) Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol 50:1884–1893
Dai W, Field LJ, Rubart M, Reuter S, Hale SL et al (2007) Survival and maturation of human embryonic stem cell-derived cardiomyocytes in rat hearts. J Mol Cell Cardiol 43:504–516
Huber I, Itzhaki I, Caspi O, Arbel G, Tzukerman M et al (2007) Identification and selection of cardiomyocytes during human embryonic stem cell differentiation. FASEB J 21:2551–2563
Kehat I, Khimovich L, Caspi O, Gepstein A, Shofti R et al (2004) Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol 22:1282–1289
Laflamme MA, Gold J, Xu C, Hassanipour M, Rosler E et al (2005) Formation of human myocardium in the rat heart from human embryonic stem cells. Am J Pathol 167:663–671
Kofidis T, Lebl DR, Swijnenburg RJ, Greeve JM, Klima U et al (2006) Allopurinol/uricase and ibuprofen enhance engraftment of cardiomyocyte-enriched human embryonic stem cells and improve cardiac function following myocardial injury. Eur J Cardiothorac Surg 29:50–55
Leor J, Gerecht S, Cohen S, Miller L, Holbova R et al (2007) Human embryonic stem cell transplantation to repair the infarcted myocardium. Heart 93:1278–1284
van Laake LW, Passier R, Doevendans PA, Mummery CL (2008) Human embryonic stem cell-derived cardiomyocytes and cardiac repair in rodents. Circ Res 102:1008–1010
van Laake LW, Passier R, Monshouwer-Kloots J, Nederhoff MG, Ward-van Oostwaard D et al (2007) Monitoring of cell therapy and assessment of cardiac function using magnetic resonance imaging in a mouse model of myocardial infarction. Nat Protoc 2:2551–2567
Halbach M, Pfannkuche K, Pillekamp F, Ziomka A, Hannes T et al (2007) Electrophysiological maturation and integration of murine fetal cardiomyocytes after transplantation. Circ Res 101:484–492
Rubart M, Pasumarthi KB, Nakajima H, Soonpaa MH, Nakajima HO et al (2003) Physiological coupling of donor and host cardiomyocytes after cellular transplantation. Circ Res 92:1217–1224
Gepstein L, Ding C, Rehemedula D, Wilson EE, Yankelson L et al (2010) In vivo assessment of the electrophysiological integration and arrhythmogenic risk of myocardial cell transplantation strategies. Stem Cells 28:2151–2161
Xue T, Cho HC, Akar FG, Tsang SY, Jones SP et al (2005) Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers. Circulation 111:11–20
Zhao T, Zhang ZN, Rong Z, Xu Y (2011) Immunogenicity of induced pluripotent stem cells. Nature 474:212–215
Wu SM, Hochedlinger K (2011) Harnessing the potential of induced pluripotent stem cells for regenerative medicine. Nat Cell Biol 13:497–505
Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A et al (2007) Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318:1920–1923
Nelson TJ, Martinez-Fernandez A, Yamada S, Perez-Terzic C, Ikeda Y et al (2009) Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation 120:408–416
Carpenter L, Carr C, Yang CT, Stuckey DJ, Clarke K et al (2012) Efficient differentiation of human induced pluripotent stem cells generates cardiac cells that provide protection following myocardial infarction in the rat. Stem Cells Dev 21:977–986
Yoshida Y, Yamanaka S (2010) Recent stem cell advances: induced pluripotent stem cells for disease modeling and stem cell-based regeneration. Circulation 122:80–87
Ben-David U, Benvenisty N (2011) The tumorigenicity of human embryonic and induced pluripotent stem cells. Nat Rev Cancer 11:268–277
Nussbaum J, Minami E, Laflamme MA, Virag JA, Ware CB et al (2007) Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response. FASEB J 21:1345–1357
Behfar A, Perez-Terzic C, Faustino RS, Arrell DK, Hodgson DM et al (2007) Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. J Exp Med 204:405–420
Tang C, Lee AS, Volkmer JP, Sahoo D, Nag D et al (2011) An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. Nat Biotechnol 29:829–834
Anderson D, Self T, Mellor IR, Goh G, Hill SJ et al (2007) Transgenic enrichment of cardiomyocytes from human embryonic stem cells. Mol Ther 15:2027–2036
Hattori F, Chen H, Yamashita H, Tohyama S, Satoh YS et al (2010) Nongenetic method for purifying stem cell-derived cardiomyocytes. Nat Methods 7:61–66
Klug MG, Soonpaa MH, Koh GY, Field LJ (1996) Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafts. J Clin Invest 98:216–224
Elliott DA, Braam SR, Koutsis K, Ng ES, Jenny R et al (2011) NKX2-5(eGFP/w) hESCs for isolation of human cardiac progenitors and cardiomyocytes. Nat Methods 8:1037–1040
van Laake LW, Qian L, Cheng P, Huang Y, Hsiao EC et al (2010) Reporter-based isolation of induced pluripotent stem cell- and embryonic stem cell-derived cardiac progenitors reveals limited gene expression variance. Circ Res 107:340–347
Van Hoof D, Dormeyer W, Braam SR, Passier R, Monshouwer-Kloots J et al (2010) Identification of cell surface proteins for antibody-based selection of human embryonic stem cell-derived cardiomyocytes. J Proteome Res 9:1610–1618
Dubois NC, Craft AM, Sharma P, Elliott DA, Stanley EG et al (2011) SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells. Nat Biotechnol 29:1011–1018
Uosaki H, Fukushima H, Takeuchi A, Matsuoka S, Nakatsuji N et al (2011) Efficient and scalable purification of cardiomyocytes from human embryonic and induced pluripotent stem cells by VCAM1 surface expression. PLoS One 6:e23657
Zhu WZ, Xie Y, Moyes KW, Gold JD, Askari B et al (2010) Neuregulin/ErbB signaling regulates cardiac subtype specification in differentiating human embryonic stem cells. Circ Res 107:776–786
Sartiani L, Bettiol E, Stillitano F, Mugelli A, Cerbai E et al (2007) Developmental changes in cardiomyocytes differentiated from human embryonic stem cells: a molecular and electrophysiological approach. Stem Cells 25:1136–1144
Tulloch NL, Muskheli V, Razumova MV, Korte FS, Regnier M et al (2011) Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ Res 109:47–59
Caspi O, Lesman A, Basevitch Y, Gepstein A, Arbel G et al (2007) Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circ Res 100:263–272
Reinecke H, Zhang M, Bartosek T, Murry CE (1999) Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts. Circulation 100:193–202
Robey TE, Saiget MK, Reinecke H, Murry CE (2008) Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol 45:567–581
Hu S, Huang M, Nguyen PK, Gong Y, Li Z et al (2011) Novel microRNA prosurvival cocktail for improving engraftment and function of cardiac progenitor cell transplantation. Circulation 124:S27–S34
Lesman A, Habib M, Caspi O, Gepstein A, Arbel G et al (2010) Transplantation of a tissue-engineered human vascularized cardiac muscle. Tissue Eng Part A 16:115–125
Stevens KR, Kreutziger KL, Dupras SK, Korte FS, Regnier M et al (2009) Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue. Proc Natl Acad Sci USA 106:16568–16573
Wu SM, Chien KR, Mummery C (2008) Origins and fates of cardiovascular progenitor cells. Cell 132:537–543
Wu SM, Fujiwara Y, Cibulsky SM, Clapham DE, Lien CL et al (2006) Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell 127:1137–1150
Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A et al (2006) Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127:1151–1165
Moretti A, Bellin M, Jung CB, Thies TM, Takashima Y et al (2010) Mouse and human induced pluripotent stem cells as a source for multipotent Isl1+ cardiovascular progenitors. FASEB J 24:700–711
Blin G, Nury D, Stefanovic S, Neri T, Guillevic O et al (2010) A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates. J Clin Invest 120:1125–1139
Habib M, Shapira-Schweitzer K, Caspi O, Gepstein A, Arbel G et al (2011) A combined cell therapy and in situ tissue-engineering approach for myocardial repair. Biomaterials 32:7514–7523
Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM et al (2008) Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med 14:213–221
Jawad H, Lyon AR, Harding SE, Ali NN, Boccaccini AR (2008) Myocardial tissue engineering. Br Med Bull 87:31–47
Masuda S, Shimizu T, Yamato M, Okano T (2008) Cell sheet engineering for heart tissue repair. Adv Drug Deliv Rev 60:277–285
Segers VF, Lee RT (2011) Biomaterials to enhance stem cell function in the heart. Circ Res 109:910–922
Zimmermann WH (2011) Embryonic and embryonic-like stem cells in heart muscle engineering. J Mol Cell Cardiol 50:320–326
Acknowledgments
We apologize to authors whose excellent works were not cited due to space restrictions. This work was supported in part by the Israel Science Foundation [1449/10], by the Israel Science Foundation and Legacy Heritage Foundation (No. 1225/09), by the Lorry Lokey research fund, and by the Nancy and Stephen Grand Philanthropic Fund.
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Zwi-Dantsis, L., Gepstein, L. Induced pluripotent stem cells for cardiac repair. Cell. Mol. Life Sci. 69, 3285–3299 (2012). https://doi.org/10.1007/s00018-012-1078-2
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DOI: https://doi.org/10.1007/s00018-012-1078-2