Reprogramming and transdifferentiation for cardiovascular development and regenerative medicine: Where do we stand?

EMBO Molecular Medicine

Volumn 7, Issue 9, 2015, Pages 1090-1103

  Ebert, Antje D ^a   Diecke, Sebastian ^b,c   Chen, Ian Y ^a   Wu, Joseph C ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^c BERLIN INSTITUTE OF HEALTH   (Germany)

Author keywords

Cardiomyocytes; Disease modeling; Genome editing; Human induced pluripotent stem cells; Tissue engineering

Indexed keywords

CARDIOVASCULAR DEVELOPMENT; CARDIOVASCULAR DISEASE; CELL SPECIFICITY; CELL TRANSDIFFERENTIATION; CELL TRANSFORMATION; GENETIC ENGINEERING; HEART DEVELOPMENT; HEART INFARCTION; HEART MUSCLE CELL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; NUCLEAR REPROGRAMMING; ORGANOGENESIS; PATHOGENESIS; PERSONALIZED MEDICINE; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REGENERATIVE MEDICINE; REVIEW; STEM CELL TRANSPLANTATION; TISSUE ENGINEERING; TISSUE REGENERATION; ANIMAL; CARDIAC MUSCLE CELL; CARDIOVASCULAR DISEASES; DISEASE MODEL; MEDICAL RESEARCH; PHYSIOLOGY; PROCEDURES; STEM CELL; TRENDS;

ANIMALS; BIOMEDICAL RESEARCH; CARDIOVASCULAR DISEASES; CELL TRANSDIFFERENTIATION; DISEASE MODELS, ANIMAL; HUMANS; MYOCYTES, CARDIAC; REGENERATIVE MEDICINE; STEM CELLS;

EID: 84940790627     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.15252/emmm.201504395     Document Type: Review

References (171)

1. Anversa P, Kajstura J, Rota M, Leri A (2013) Regenerating new heart with stem cells. J Clin Invest 123: 62-70
2. Asimaki A, Kapoor S, Plovie E, Karin Arndt A, Adams E, Liu Z, James CA, Judge DP, Calkins H, Churko J et al (2014) Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy. Sci Transl Med 6: 240ra274
3. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H et al (2002) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 106: 3009-3017
4. Ban H, Nishishita N, Fusaki N, Tabata T, Saeki K, Shikamura M, Takada N, Inoue M, Hasegawa M, Kawamata S et al (2011) Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors. Proc Natl Acad Sci USA 108: 14234-14239
5. Bar-Nur O, Russ HA, Efrat S, Benvenisty N (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 9: 17-23
6. Bedada FB, Chan SS, Metzger SK, Zhang L, Zhang J, Garry DJ, Kamp TJ, Kyba M, Metzger JM (2014) Acquisition of a quantitative, stoichiometrically conserved ratiometric marker of maturation status in stem cell-derived cardiac myocytes. Stem Cell Reports 3: 594-605
7. van Berlo JH, Molkentin JD (2014) An emerging consensus on cardiac regeneration. Nat Med 20: 1386-1393
8. Benson DW, Wang DW, Dyment M, Knilans TK, Fish FA, Strieper MJ, Rhodes TH, George AL Jr (2003) Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest 112: 1019-1028
9. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324: 98-102
10. Bett GC, Kaplan AD, Lis A, Cimato TR, Tzanakakis ES, Zhou Q, Morales MJ, Rasmusson RL (2013) Electronic "expression" of the inward rectifier in cardiocytes derived from human-induced pluripotent stem cells. Heart Rhythm 10: 1903-1910
11. Bevilacqua A, Willis MS, Bultman SJ (2014) SWI/SNF chromatin-remodeling complexes in cardiovascular development and disease. Cardiovasc Pathol 23: 85-91
12. Boon RA, Dimmeler S (2015) MicroRNAs in myocardial infarction. Nat Rev Cardiol 12: 135-142
13. 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
14. Burridge PW, Matsa E, Shukla P, Lin ZC, Churko JM, Ebert AD, Lan F, Diecke S, Huber B, Mordwinkin NM et al (2014) Chemically defined generation of human cardiomyocytes. Nat Methods 11: 855-860
15. Carey BW, Markoulaki S, Hanna JH, Faddah DA, Buganim Y, Kim J, Ganz K, Steine EJ, Cassady JP, Creyghton MP et al (2011) Reprogramming factor stoichiometry influences the epigenetic state and biological properties of induced pluripotent stem cells. Cell Stem Cell 9: 588-598
16. Carvajal-Vergara X, Sevilla A, D'Souza SL, Ang YS, Schaniel C, Lee DF, Yang L, Kaplan AD, Adler ED, Rozov R et al (2010) Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 465: 808-812
17. Caspi O, Huber I, Gepstein A, Arbel G, Maizels L, Boulos M, Gepstein L (2013) Modeling of arrhythmogenic right ventricular cardiomyopathy with human induced pluripotent stem cells. Circ Cardiovasc Genet 6: 557-568
18. Caspi O, Huber I, Kehat I, Habib M, Arbel G, Gepstein A, Yankelson L, Aronson D, Beyar R, Gepstein L (2007) Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol 50: 1884-1893
19. Chang CP, Bruneau BG (2012) Epigenetics and cardiovascular development. Annu Rev Physiol 74: 41-68
20. Chen G, Gulbranson DR, Hou Z, Bolin JM, Ruotti V, Probasco MD, Smuga-Otto K, Howden SE, Diol NR, Propson NE et al (2011) Chemically defined conditions for human iPSC derivation and culture. Nat Methods 8: 424-429
21. Chen JX, Krane M, Deutsch MA, Wang L, Rav-Acha M, Gregoire S, Engels MC, Rajarajan K, Karra R, Abel ED et al (2012) Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5. Circ Res 111: 50-55
22. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, Moya A, Borggrefe M, Breithardt G et al (1998) Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 392: 293-296
23. Chong JJ, Yang X, Don CW, Minami E, Liu YW, Weyers JJ, Mahoney WM, Van Biber B, Cook SM, Palpant NJ et al (2014) Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510: 273-277
24. Chugh AR, Beache GM, Loughran JH, Mewton N, Elmore JB, Kajstura J, Pappas P, Tatooles A, Stoddard MF, Lima JA et al (2012) 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
25. Cordes KR, Srivastava D (2009) MicroRNA regulation of cardiovascular development. Circ Res 104: 724-732
26. Davis RP, Casini S, van den Berg CW, Hoekstra M, Remme CA, Dambrot C, Salvatori D, Oostwaard DW, Wilde AA, Bezzina CR et al (2012) Cardiomyocytes derived from pluripotent stem cells recapitulate electrophysiological characteristics of an overlap syndrome of cardiac sodium channel disease. Circulation 125: 3079-3091
27. De Los Angeles A, Loh YH, Tesar PJ, Daley GQ (2012) Accessing naive human pluripotency. Curr Opin Genet Dev 22: 272-282
28. Deuse T, Wang D, Stubbendorff M, Itagaki R, Grabosch A, Greaves LC, Alawi M, Grunewald A, Hu X, Hua X et al (2015) SCNT-derived ESCs with mismatched mitochondria trigger an immune response in allogeneic hosts. Cell Stem Cell 16: 33-38
29. Diecke S, Lu J, Lee J, Termglinchan V, Kooreman NG, Burridge PW, Ebert AD, Churko JM, Sharma A, Kay MA et al (2015) Novel codon-optimized mini-intronic plasmid for efficient, inexpensive, and xeno-free induction of pluripotency. Sci Rep 5: 8081
30. Dimmeler S, Zeiher AM, Schneider MD (2005) Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 115: 572-583
31. Ding Q, Lee YK, Schaefer EA, Peters DT, Veres A, Kim K, Kuperwasser N, Motola DL, Meissner TB, Hendriks WT et al (2013) A TALEN genome-editing system for generating human stem cell-based disease models. Cell Stem Cell 12: 238-251
32. Dorn GW 2nd (2009) Novel pharmacotherapies to abrogate postinfarction ventricular remodeling. Nat Rev Cardiol 6: 283-291
33. Duncker DJ, Bakkers J, Brundel BJ, Robbins J, Tardiff JC, Carrier L (2015) Animal and in silico models for the study of sarcomeric cardiomyopathies. Cardiovasc Res 105: 439-448
34. Ebert AD, Kodo K, Liang P, Wu H, Huber BC, Riegler J, Churko J, Lee J, de Almeida P, Lan F et al (2014) Characterization of the molecular mechanisms underlying increased ischemic damage in the aldehyde dehydrogenase 2 genetic polymorphism using a human induced pluripotent stem cell model system. Sci Transl Med 6: 255ra130
35. Ebert AD, Liang P, Wu JC (2012) Induced pluripotent stem cells as a disease modeling and drug screening platform. J Cardiovasc Pharmacol 60: 408-416
36. Efe JA, Hilcove S, Kim J, Zhou H, Ouyang K, Wang G, Chen J, Ding S (2011) Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat Cell Biol 13: 215-222
37. Emmert MY, Hitchcock RW, Hoerstrup SP (2014) Cell therapy, 3D culture systems and tissue engineering for cardiac regeneration. Adv Drug Deliv Rev 69-70: 254-269
38. Fiedler LR, Maifoshie E, Schneider MD (2014) Mouse models of heart failure: cell signaling and cell survival. Curr Top Dev Biol 109: 171-247
39. Fu JD, Rushing SN, Lieu DK, Chan CW, Kong CW, Geng L, Wilson KD, Chiamvimonvat N, Boheler KR, Wu JC et al (2011) Distinct roles of microRNA-1 and -499 in ventricular specification and functional maturation of human embryonic stem cell-derived cardiomyocytes. PLoS ONE 6: e27417
40. Fu JD, Stone NR, Liu L, Spencer CI, Qian L, Hayashi Y, Delgado-Olguin P, Ding S, Bruneau BG, Srivastava D (2013) Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state. Stem Cell Reports 1: 235-247
41. 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. Proc Jpn Acad Ser B Phys Biol Sci 85: 348-362
42. Gafni O, Weinberger L, Mansour AA, Manor YS, Chomsky E, Ben-Yosef D, Kalma Y, Viukov S, Maza I, Zviran A et al (2013) Derivation of novel human ground state naive pluripotent stem cells. Nature 504: 282-286
43. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS et al (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11: 367-368
44. Gu M, Nguyen PK, Lee AS, Xu D, Hu S, Plews JR, Han L, Huber BC, Lee WH, Gong Y et al (2012) Microfluidic single-cell analysis shows that porcine induced pluripotent stem cell-derived endothelial cells improve myocardial function by paracrine activation. Circ Res 111: 882-893
45. Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, Brinker JA et al (2012) Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 308: 2369-2379
46. Hendel A, Fine EJ, Bao G, Porteus MH (2015) Quantifying on- and off-target genome editing. Trends Biotechnol 33: 132-140
47. Hirai H, Firpo M, Kikyo N (2012) Establishment of LIF-dependent human iPS cells closely related to basic FGF-dependent authentic iPS cells. PLoS ONE 7: e39022
48. Hirt MN, Boeddinghaus J, Mitchell A, Schaaf S, Bornchen C, Muller C, Schulz H, Hubner N, Stenzig J, Stoehr A et al (2014a) Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation. J Mol Cell Cardiol 74: 151-161
49. Hirt MN, Hansen A, Eschenhagen T (2014b) Cardiac tissue engineering: state of the art. Circ Res 114: 354-367
50. Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC et al (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29: 731-734
51. Honda A, Hatori M, Hirose M, Honda C, Izu H, Inoue K, Hirasawa R, Matoba S, Togayachi S, Miyoshi H et al (2013) Naive-like conversion overcomes the limited differentiation capacity of induced pluripotent stem cells. J Biol Chem 288: 26157-26166
52. Houser SR, Margulies KB, Murphy AM, Spinale FG, Francis GS, Prabhu SD, Rockman HA, Kass DA, Molkentin JD, Sussman MA et al (2012) Animal models of heart failure: a scientific statement from the American Heart Association. Circ Res 111: 131-150
53. Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, Hu Y, Wang X, Hui L (2011) Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475: 386-389
54. Huber BC, Ransohoff JD, Ransohoff KJ, Riegler J, Ebert A, Kodo K, Gong Y, Sanchez-Freire V, Dey D, Kooreman NG et al (2013) Costimulation-adhesion blockade is superior to cyclosporine A and prednisone immunosuppressive therapy for preventing rejection of differentiated human embryonic stem cells following transplantation. Stem Cells 31: 2354-2363
55. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D (2010) Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142: 375-386
56. Inagawa K, Miyamoto K, Yamakawa H, Muraoka N, Sadahiro T, Umei T, Wada R, Katsumata Y, Kaneda R, Nakade K et al (2012) Induction of cardiomyocyte-like cells in infarct hearts by gene transfer of Gata4, Mef2c, and Tbx5. Circ Res 111: 1147-1156
57. Islas JF, Liu Y, Weng KC, Robertson MJ, Zhang S, Prejusa A, Harger J, Tikhomirova D, Chopra M, Iyer D et al (2012) Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors. Proc Natl Acad Sci USA 109: 13016-13021
58. Itzhaki I, Maizels L, Huber I, Zwi-Dantsis L, Caspi O, Winterstern A, Feldman O, Gepstein A, Arbel G, Hammerman H et al (2011) Modelling the long QT syndrome with induced pluripotent stem cells. Nature 471: 225-229
59. Jayawardena T, Mirotsou M, Dzau VJ (2014) Direct reprogramming of cardiac fibroblasts to cardiomyocytes using microRNAs. Methods Mol Biol 1150: 263-272
60. Jayawardena TM, Egemnazarov B, Finch EA, Zhang L, Payne JA, Pandya K, Zhang Z, Rosenberg P, Mirotsou M, Dzau VJ (2012) MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res 110: 1465-1473
61. Jayawardena TM, Finch EA, Zhang L, Zhang H, Hodgkinson CP, Pratt RE, Rosenberg PB, Mirotsou M, Dzau VJ (2015) MicroRNA induced cardiac reprogramming in vivo: evidence for mature cardiac myocytes and improved cardiac function. Circ Res 116: 418-424
62. Jia F, Wilson KD, Sun N, Gupta DM, Huang M, Li Z, Panetta NJ, Chen ZY, Robbins RC, Kay MA et al (2010) A nonviral minicircle vector for deriving human iPS cells. Nat Methods 7: 197-199
63. Kamakura T, Makiyama T, Sasaki K, Yoshida Y, Wuriyanghai Y, Chen J, Hattori T, Ohno S, Kita T, Horie M et al (2013) Ultrastructural maturation of human-induced pluripotent stem cell-derived cardiomyocytes in a long-term culture. Circ J 77: 1307-1314
64. Karakikes I, Ameen M, Termglinchan V, Wu JC (2015) Human induced pluripotent stem cell-derived cardiomyocytes: insights into molecular, cellular, and functional phenotypes. Circ Res 117: 80-88
65. Karantalis V, DiFede DL, Gerstenblith G, Pham S, Symes J, Zambrano JP, Fishman J, Pattany P, McNiece I, Conte J et al (2014) Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: the Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial. Circ Res 114: 1302-1310
66. Kass RS (2005) The channelopathies: novel insights into molecular and genetic mechanisms of human disease. J Clin Invest 115: 1986-1989
67. Kattman SJ, Witty AD, Gagliardi M, Dubois NC, Niapour M, Hotta A, Ellis J, Keller G (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
68. Kawamura M, Miyagawa S, Miki K, Saito A, Fukushima S, Higuchi T, Kawamura T, Kuratani T, Daimon T, Shimizu T et al (2012) Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation 126: S29-S37
69. Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M, Gepstein A, Livne E, Binah O, Itskovitz-Eldor J, Gepstein L (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 108: 407-414
70. Kehat I, Khimovich L, Caspi O, Gepstein A, Shofti R, Arbel G, Huber I, Satin J, Itskovitz-Eldor J, Gepstein L (2004) Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol 22: 1282-1289
71. Kim C, Wong J, Wen J, Wang S, Wang C, Spiering S, Kan NG, Forcales S, Puri PL, Leone TC et al (2013) Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs. Nature 494: 105-110
72. Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R et al (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4: 472-476
73. Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich LI et al (2010) Epigenetic memory in induced pluripotent stem cells. Nature 467: 285-290
74. Kim K, Zhao R, Doi A, Ng K, Unternaehrer J, Cahan P, Huo H, Loh YH, Aryee MJ, Lensch MW et al (2011) Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat Biotechnol 29: 1117-1119
75. Korf-Klingebiel M, Reboll MR, Klede S, Brod T, Pich A, Polten F, Napp LC, Bauersachs J, Ganser A, Brinkmann E et al (2015) Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction. Nat Med 21: 140-149
76. 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
77. Ladewig J, Koch P, Brustle O (2013) Leveling Waddington: the emergence of direct programming and the loss of cell fate hierarchies. Nat Rev Mol Cell Biol 14: 225-236
78. Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, Reinecke H, Xu C, Hassanipour M, Police S 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
79. Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473: 326-335
80. Lan F, Lee AS, Liang P, Sanchez-Freire V, Nguyen PK, Wang L, Han L, Yen M, Wang Y, Sun N et al (2013) Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent stem cells. Cell Stem Cell 12: 101-113
81. Lee AS, Tang C, Cao F, Xie X, van der Bogt K, Hwang A, Connolly AJ, Robbins RC, Wu JC (2009) Effects of cell number on teratoma formation by human embryonic stem cells. Cell Cycle 8: 2608-2612
82. Lee AS, Tang C, Rao MS, Weissman IL, Wu JC (2013) Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med 19: 998-1004
83. Lehnart SE, Ackerman MJ, Benson DW Jr, Brugada R, Clancy CE, Donahue JK, George AL Jr, Grant AO, Groft SC, January CT et al (2007) Inherited arrhythmias: a National Heart, Lung, and Blood Institute and Office of Rare Diseases workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardiomyopathies of gene mutations affecting ion channel function. Circulation 116: 2325-2345
84. 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
85. Li Z, Han Z, Wu JC (2009a) Transplantation of human embryonic stem cell-derived endothelial cells for vascular diseases. J Cell Biochem 106: 194-199
86. Li Z, Lee A, Huang M, Chun H, Chung J, Chu P, Hoyt G, Yang P, Rosenberg J, Robbins RC et al (2009b) Imaging survival and function of transplanted cardiac resident stem cells. J Am Coll Cardiol 53: 1229-1240
87. Lian Q, Zhang Y, Zhang J, Zhang HK, Wu X, Zhang Y, Lam FF, Kang S, Xia JC, Lai WH et al (2010) Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation 121: 1113-1123
88. Lian X, Hsiao C, Wilson G, Zhu K, Hazeltine LB, Azarin SM, Raval KK, Zhang J, Kamp TJ, Palecek SP (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci USA 109: E1848-E1857
89. Liang P, Lan F, Lee AS, Gong T, Sanchez-Freire V, Wang Y, Diecke S, Sallam K, Knowles JW, Wang PJ et al (2013) Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation 127: 1677-1691
90. Lieu DK, Fu JD, Chiamvimonvat N, Tung KC, McNerney GP, Huser T, Keller G, Kong CW, Li RA (2013) Mechanism-based facilitated maturation of human pluripotent stem cell-derived cardiomyocytes. Circ Arrhythm Electrophysiol 6: 191-201
91. Lin SL, Chang DC, Lin CH, Ying SY, Leu D, Wu DT (2011) Regulation of somatic cell reprogramming through inducible mir-302 expression. Nucleic Acids Res 39: 1054-1065
92. Lin Y, Fine EJ, Zheng Z, Antico CJ, Voit RA, Porteus MH, Cradick TJ, Bao G (2014) SAPTA: a new design tool for improving TALE nuclease activity. Nucleic Acids Res 42: e47
93. Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Antosiewicz-Bourget J, O'Malley R, Castanon R, Klugman S et al (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471: 68-73
94. Liu J, Narsinh KH, Lan F, Wang L, Nguyen PK, Hu S, Lee A, Han L, Gong Y, Huang M et al (2012) Early stem cell engraftment predicts late cardiac functional recovery: preclinical insights from molecular imaging. Circ Cardiovasc Imaging 5: 481-490
95. + stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 115: 3165-3172
96. Maillet M, van Berlo JH, Molkentin JD (2013) Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol 14: 38-48
97. Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, Czer LS, Marban L, Mendizabal A, Johnston PV et al (2012) Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 379: 895-904
98. Matsa E, Burridge PW, Wu JC (2014) Human stem cells for modeling heart disease and for drug discovery. Sci Transl Med 6: 239 ps236
99. McNally EM, Golbus JR, Puckelwartz MJ (2013) Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest 123: 19-26
100. Menasche P, Vanneaux V, Hagege A, Bel A, Cholley B, Cacciapuoti I, Parouchev A, Benhamouda N, Tachdjian G, Tosca L et al (2015) Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. Eur Heart J 36: 2011-2017
101. Moretti A, Bellin M, Welling A, Jung CB, Lam JT, Bott-Flugel L, Dorn T, Goedel A, Hohnke C, Hofmann F et al (2010) Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med 363: 1397-1409
102. Mummery C, van der Heyden MA, de Boer TP, Passier R, Ward D, van den Brink S, van Rooijen M, van de Stolpe A (2007) Cardiomyocytes from human and mouse embryonic stem cells. Methods Mol Med 140: 249-272
103. Muraoka N, Yamakawa H, Miyamoto K, Sadahiro T, Umei T, Isomi M, Nakashima H, Akiyama M, Wada R, Inagawa K et al (2014) MiR-133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures. EMBO J 33: 1565-1581
104. Naito H, Melnychenko I, Didie M, Schneiderbanger K, Schubert P, Rosenkranz S, Eschenhagen T, Zimmermann WH (2006) Optimizing engineered heart tissue for therapeutic applications as surrogate heart muscle. Circulation 114: I72-I78
105. Nam YJ, Lubczyk C, Bhakta M, Zang T, Fernandez-Perez A, McAnally J, Bassel-Duby R, Olson EN, Munshi NV (2014) Induction of diverse cardiac cell types by reprogramming fibroblasts with cardiac transcription factors. Development 141: 4267-4278
106. Nam YJ, Song K, Luo X, Daniel E, Lambeth K, West K, Hill JA, DiMaio JM, Baker LA, Bassel-Duby R et al (2013) Reprogramming of human fibroblasts toward a cardiac fate. Proc Natl Acad Sci USA 110: 5588-5593
107. Navarrete EG, Liang P, Lan F, Sanchez-Freire V, Simmons C, Gong T, Sharma A, Burridge PW, Patlolla B, Lee AS et al (2013) Screening drug-induced arrhythmia using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays. Circulation 128: S3-S13
108. Neofytou E, O'Brien CG, Couture LA, Wu JC (2015) Hurdles to clinical translation of human induced pluripotent stem cells. J Clin Invest 125: 2551-2557
109. Nguyen PK, Riegler J, Wu JC (2014) Stem cell imaging: from bench to bedside. Cell Stem Cell 14: 431-444
110. Nichols J, Smith A (2009) Naive and primed pluripotent states. Cell Stem Cell 4: 487-492
111. Nunes SS, Miklas JW, Liu J, Aschar-Sobbi R, Xiao Y, Zhang B, Jiang J, Masse S, Gagliardi M, Hsieh A et al (2013) Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat Methods 10: 781-787
112. Ohi Y, Qin H, Hong C, Blouin L, Polo JM, Guo T, Qi Z, Downey SL, Manos PD, Rossi DJ et al (2011) Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat Cell Biol 13: 541-549
113. Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322: 949-953
114. Ong SG, Lee WH, Kodo K, Wu JC (2015) MicroRNA-mediated regulation of differentiation and trans-differentiation in stem cells. Adv Drug Deliv Rev 88: 3-15
115. Paige SL, Osugi T, Afanasiev OK, Pabon L, Reinecke H, Murry CE (2010) Endogenous Wnt/beta-catenin signaling is required for cardiac differentiation in human embryonic stem cells. PLoS ONE 5: e11134
116. Parmacek MS, Epstein JA (2009) Cardiomyocyte renewal. N Engl J Med 361: 86-88
117. Pearl JI, Kean LS, Davis MM, Wu JC (2012) Pluripotent stem cells: immune to the immune system? Sci Transl Med 4: 164ps125
118. Pearl JI, Lee AS, Leveson-Gower DB, Sun N, Ghosh Z, Lan F, Ransohoff J, Negrin RS, Davis MM, Wu JC (2011) Short-term immunosuppression promotes engraftment of embryonic and induced pluripotent stem cells. Cell Stem Cell 8: 309-317
119. Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, Sadek HA (2011) Transient regenerative potential of the neonatal mouse heart. Science 331: 1078-1080
120. Protze S, Khattak S, Poulet C, Lindemann D, Tanaka EM, Ravens U (2012) A new approach to transcription factor screening for reprogramming of fibroblasts to cardiomyocyte-like cells. J Mol Cell Cardiol 53: 323-332
121. Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, Conway SJ, Fu JD, Srivastava D (2012) In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 485: 593-598
122. Qian L, Srivastava D (2013) Direct cardiac reprogramming: from developmental biology to cardiac regeneration. Circ Res 113: 915-921
123. Rais Y, Zviran A, Geula S, Gafni O, Chomsky E, Viukov S, Mansour AA, Caspi I, Krupalnik V, Zerbib M et al (2013) Deterministic direct reprogramming of somatic cells to pluripotency. Nature 502: 65-70
124. Rao C, Prodromakis T, Kolker L, Chaudhry UA, Trantidou T, Sridhar A, Weekes C, Camelliti P, Harding SE, Darzi A et al (2013) The effect of microgrooved culture substrates on calcium cycling of cardiac myocytes derived from human induced pluripotent stem cells. Biomaterials 34: 2399-2411
125. Ribeiro MC, Tertoolen LG, Guadix JA, Bellin M, Kosmidis G, D'Aniello C, Monshouwer-Kloots J, Goumans MJ, Wang YL, Feinberg AW et al (2015) Functional maturation of human pluripotent stem cell derived cardiomyocytes in vitro - Correlation between contraction force and electrophysiology. Biomaterials 51: 138-150
126. Riegler J, Gillich A, Shen Q, Gold JD, Wu JC (2014) Cardiac tissue slice transplantation as a model to assess tissue-engineered graft thickness, survival, and function. Circulation 130: S77-S86
127. Sallam K, Li Y, Sager PT, Houser SR, Wu JC (2015) Finding the rhythm of sudden cardiac death: new opportunities using induced pluripotent stem cell-derived cardiomyocytes. Circ Res 116: 1989-2004
128. Sanchez-Freire V, Lee AS, Hu S, Abilez OJ, Liang P, Lan F, Huber BC, Ong SG, Hong WX, Huang M et al (2014) Effect of human donor cell source on differentiation and function of cardiac induced pluripotent stem cells. J Am Coll Cardiol 64: 436-448
129. Sander JD, Joung JK (2014) CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol 32: 347-355
130. Sanganalmath SK, Bolli R (2013) Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circ Res 113: 810-834
131. Sartiani L, Bettiol E, Stillitano F, Mugelli A, Cerbai E, Jaconi ME (2007) Developmental changes in cardiomyocytes differentiated from human embryonic stem cells: a molecular and electrophysiological approach. Stem Cells 25: 1136-1144
132. Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H et al (2004) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 44: 1690-1699
133. Schwartz PJ, Priori SG, Dumaine R, Napolitano C, Antzelevitch C, Stramba-Badiale M, Richard TA, Berti MR, Bloise R (2000) A molecular link between the sudden infant death syndrome and the long-QT syndrome. N Engl J Med 343: 262-267
134. Sekine H, Shimizu T, Hobo K, Sekiya S, Yang J, Yamato M, Kurosawa H, Kobayashi E, Okano T (2008) Endothelial cell coculture within tissue-engineered cardiomyocyte sheets enhances neovascularization and improves cardiac function of ischemic hearts. Circulation 118: S145-S152
135. Sekine H, Shimizu T, Sakaguchi K, Dobashi I, Wada M, Yamato M, Kobayashi E, Umezu M, Okano T (2013) In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels. Nat Commun 4: 1399
136. Sharma A, Marceau C, Hamaguchi R, Burridge PW, Rajarajan K, Churko JM, Wu H, Sallam KI, Matsa E, Sturzu AC et al (2014) Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform. Circ Res 115: 556-566
137. Smart N, Bollini S, Dube KN, Vieira JM, Zhou B, Davidson S, Yellon D, Riegler J, Price AN, Lythgoe MF et al (2011) De novo cardiomyocytes from within the activated adult heart after injury. Nature 474: 640-644
138. Smart N, Dube KN, Riley PR (2010) Identification of Thymosin beta4 as an effector of Hand1-mediated vascular development. Nat Commun 1: 46
139. Sun N, Yazawa M, Liu J, Han L, Sanchez-Freire V, Abilez OJ, Navarrete EG, Hu S, Wang L, Lee A et al (2012) Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy. Sci Transl Med 4: 130ra147
140. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663-676
141. Takeuchi JK, Bruneau BG (2009) Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 459: 708-711
142. Tang C, Lee AS, Volkmer JP, Sahoo D, Nag D, Mosley AR, Inlay MA, Ardehali R, Chavez SL, Pera RR 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
143. Taylor CJ, Peacock S, Chaudhry AN, Bradley JA, Bolton EM (2012) Generating an iPSC bank for HLA-matched tissue transplantation based on known donor and recipient HLA types. Cell Stem Cell 11: 147-152
144. Tee R, Morrison WA, Dusting GJ, Liu GS, Choi YS, Hsiao ST, Dilley RJ (2012) Transplantation of engineered cardiac muscle flaps in syngeneic rats. Tissue Eng Part A 18: 1992-1999
145. Theunissen TW, Jaenisch R (2014) Molecular control of induced pluripotency. Cell Stem Cell 14: 720-734
146. Theunissen TW, Powell BE, Wang H, Mitalipova M, Faddah DA, Reddy J, Fan ZP, Maetzel D, Ganz K, Shi L et al (2014) Systematic identification of culture conditions for induction and maintenance of naive human pluripotency. Cell Stem Cell 15: 471-487
147. Tiburcy M, Didie M, Boy O, Christalla P, Doker S, Naito H, Karikkineth BC, El-Armouche A, Grimm M, Nose M et al (2011) Terminal differentiation, advanced organotypic maturation, and modeling of hypertrophic growth in engineered heart tissue. Circ Res 109: 1105-1114
148. Traverse JH, Henry TD, Pepine CJ, Willerson JT, Zhao DX, Ellis SG, Forder JR, Anderson RD, Hatzopoulos AK, Penn MS et al (2012) Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial. JAMA 308: 2380-2389
149. Tulloch NL, Muskheli V, Razumova MV, Korte FS, Regnier M, Hauch KD, Pabon L, Reinecke H, Murry CE (2011) Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ Res 109: 47-59
150. Verdouw PD, van den Doel MA, de Zeeuw S, Duncker DJ (1998) Animal models in the study of myocardial ischaemia and ischaemic syndromes. Cardiovasc Res 39: 121-135
151. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M (2010) Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463: 1035-1041
152. + cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation 128: S42-S49
153. Wada R, Muraoka N, Inagawa K, Yamakawa H, Miyamoto K, Sadahiro T, Umei T, Kaneda R, Suzuki T, Kamiya K et al (2013) Induction of human cardiomyocyte-like cells from fibroblasts by defined factors. Proc Natl Acad Sci USA 110: 12667-12672
154. Wang L, Liu Z, Yin C, Asfour H, Chen O, Li Y, Bursac N, Liu J, Qian L (2015) Stoichiometry of Gata4, Mef2c, and Tbx5 influences the efficiency and quality of induced cardiac myocyte reprogramming. Circ Res 116: 237-244
155. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT (1995) SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 80: 805-811
156. Wang QT (2012) Epigenetic regulation of cardiac development and function by polycomb group and trithorax group proteins. Dev Dyn 241: 1021-1033
157. Wang Y, Liang P, Lan F, Wu H, Lisowski L, Gu M, Hu S, Kay MA, Urnov FD, Shinnawi R et al (2014) Genome editing of isogenic human induced pluripotent stem cells recapitulates long QT phenotype for drug testing. J Am Coll Cardiol 64: 451-459
158. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A et al (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7: 618-630
159. Wilson KD, Wu JC (2015) Induced pluripotent stem cells. JAMA 313: 1613-1614
160. Yang X, Pabon L, Murry CE (2014) Engineering adolescence: maturation of human pluripotent stem cell-derived cardiomyocytes. Circ Res 114: 511-523
161. Yazawa M, Hsueh B, Jia X, Pasca AM, Bernstein JA, Hallmayer J, Dolmetsch RE (2011) Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature 471: 230-234
162. Ye L, Chang YH, Xiong Q, Zhang P, Zhang L, Somasundaram P, Lepley M, Swingen C, Su L, Wendel JS et al (2014) Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. Cell Stem Cell 15: 750-761
163. Ye L, Zimmermann WH, Garry DJ, Zhang J (2013) Patching the heart: cardiac repair from within and outside. Circ Res 113: 922-932
164. Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, Thomson JA (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324: 797-801
165. Zangi L, Lui KO, von Gise A, Ma Q, Ebina W, Ptaszek LM, Spater D, Xu H, Tabebordbar M, Gorbatov R et al (2013) Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction. Nat Biotechnol 31: 898-907
166. Zhang D, Shadrin IY, Lam J, Xian HQ, Snodgrass HR, Bursac N (2013) Tissue-engineered cardiac patch for advanced functional maturation of human ESC-derived cardiomyocytes. Biomaterials 34: 5813-5820
167. Zhang J, Klos M, Wilson GF, Herman AM, Lian X, Raval KK, Barron MR, Hou L, Soerens AG, Yu J et al (2012) Extracellular matrix promotes highly efficient cardiac differentiation of human pluripotent stem cells: the matrix sandwich method. Circ Res 111: 1125-1136
168. Zhou W, Freed CR (2009) Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells 27: 2667-2674
169. Zimmermann WH (2013) Biomechanical regulation of in vitro cardiogenesis for tissue-engineered heart repair. Stem Cell Res Ther 4: 137
170. Zimmermann WH, Melnychenko I, Wasmeier G, Didie M, Naito H, Nixdorff U, Hess A, Budinsky L, Brune K, Michaelis B et al (2006) Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med 12: 452-458
171. Zimmermann WH, Schneiderbanger K, Schubert P, Didie M, Munzel F, Heubach JF, Kostin S, Neuhuber WL, Eschenhagen T (2002) Tissue engineering of a differentiated cardiac muscle construct. Circ Res 90: 223-230