Mending a Faltering Heart

Circulation Research

Volumn 118, Issue 2, 2016, Pages 344-351

  Li, Mo ^a,b   Izpisua Belmonte, Juan Carlos ^a  

^a SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^b CATHOLIC UNIVERSITY OF MURCIA   (Spain)

Author keywords

cellular reprogramming; induced pluripotent stem cells; myocardial infarction; myocardial ischemia; myocytes, cardiac

Indexed keywords

ANIMAL; CARDIAC MUSCLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CONVALESCENCE; DISEASE MODEL; GENETICS; HUMAN; METABOLISM; MYOCARDIAL INFARCTION; NUCLEAR REPROGRAMMING; PATHOLOGY; PATHOPHYSIOLOGY; PROCEDURES; REGENERATION; STEM CELL TRANSPLANTATION;

ANIMALS; CELL DIFFERENTIATION; CELL PROLIFERATION; CELLULAR REPROGRAMMING; DISEASE MODELS, ANIMAL; HUMANS; MYOCARDIAL INFARCTION; MYOCARDIUM; RECOVERY OF FUNCTION; REGENERATION; STEM CELL TRANSPLANTATION;

EID: 84955277709     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.115.306820     Document Type: Review

References (101)

1. Baudino TA, Carver W, Giles W, Borg TK., Cardiac fibroblasts: friend or foe? Am J Physiol Heart Circ Physiol 2006;291:H1015-H1026. doi: 10.1152/ajpheart.00023.2006.
2. Yuan P, Ma X., Endothelial cells facilitate cell-based cardiac repair: progress and challenge. Curr Stem Cell Res Ther 2014;9 415:423
3. Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, Nadal-Ginard B, Silvestri F, Leri A, Beltrami CA, Anversa P., Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 2001-344 1750 1757. doi: 10.1056/NEJM200106073442303.
4. Olivetti G, Cigola E, Maestri R, Corradi D, Lagrasta C, Gambert SR, Anversa P., Aging, cardiac hypertrophy and ischemic cardiomyopathy do not affect the proportion of mononucleated and multinucleated myocytes in the human heart. J Mol Cell Cardiol 1996;28:1463-1477. doi: 10.1006/jmcc.1996.0137.
5. Maillet M, van Berlo JH, Molkentin JD., Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol 2013;14:38-48. doi: 10.1038/nrm3495.
6. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisén J., Evidence for cardiomyocyte renewal in humans. Science 2009;324:98-102. doi: 10.1126/science.1164680.
7. Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, Wu TD, Guerquin-Kern JL, Lechene CP, Lee RT., Mammalian heart renewal by pre-existing cardiomyocytes. Nature 2013;493:433-436. doi: 10.1038/nature11682.
8. Soonpaa MH, Field LJ., Assessment of cardiomyocyte DNA synthesis in normal and injured adult mouse hearts. Am J Physiol 1997;272:H220-H226
9. Naqvi N, Li M, Calvert JW, A proliferative burst during preadolescence establishes the final cardiomyocyte number. Cell 2014;157:795-807. doi: 10.1016/j.cell.2014.03.035.
10. Später D, Abramczuk MK, Buac K, Zangi L, Stachel MW, Clarke J, Sahara M, Ludwig A, Chien KR., A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells. Nat Cell Biol 2013;15:1098-1106. doi: 10.1038/ncb2824.
11. Liang X, Wang G, Lin L, Lowe J, Zhang Q, Bu L, Chen Y, Chen J, Sun Y, Evans SM., HCN4 dynamically marks the first heart field and conduction system precursors. Circ Res 2013;113:399-407. doi: 10.1161/CIRCRESAHA.113.301588.
12. Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz KL, Chien KR., Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 2006;127:1151-1165. doi: 10.1016/j.cell.2006.10.029.
13. Sun Y, Liang X, Najafi N, Cass M, Lin L, Cai CL, Chen J, Evans SM., Islet 1 is expressed in distinct cardiovascular lineages, including pacemaker and coronary vascular cells. Dev Biol 2007;304:286-296. doi: 10.1016/j.ydbio.2006.12.048.
14. Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao Y, Roberts DJ, Huang PL, Domian IJ, Chien KR., Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature 2009;460:113-117. doi: 10.1038/nature08191.
15. Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT., Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 2008;454:109-113. doi: 10.1038/nature07060.
16. Cai CL, Martin JC, Sun Y, Cui L, Wang L, Ouyang K, Yang L, Bu L, Liang X, Zhang X, Stallcup WB, Denton CP, McCulloch A, Chen J, Evans SM., A myocardial lineage derives from Tbx18 epicardial cells. Nature 2008;454:104-108. doi: 10.1038/nature06969.
17. Christoffels VM, Grieskamp T, Norden J, Mommersteeg MT, Rudat C, Kispert A., Tbx18 and the fate of epicardial progenitors. Nature 2009;458:E8-E9. doi: 10.1038/nature07916.
18. van Berlo JH, Molkentin JD., An emerging consensus on cardiac regeneration. Nat Med 2014;20:1386-1393. doi: 10.1038/nm.3764.
19. Keith MC, Bolli R., "String theory" of c-kit(pos) cardiac cells: a new paradigm regarding the nature of these cells that may reconcile apparently discrepant results. Circ Res 2015;116:1216-1230. doi: 10.1161/CIRCRESAHA.116.305557.
20. Chong JJ, Forte E, Harvey RP., Developmental origins and lineage descendants of endogenous adult cardiac progenitor cells. Stem Cell Res 2014;13:592-614. doi: 10.1016/j.scr.2014.09.008.
21. Sahara M, Santoro F, Chien KR., Programming and reprogramming a human heart cell. EMBO J 2015;34:710-738. doi: 10.15252/embj.201490563.
22. Smart N, Bollini S, Dubé KN, Vieira JM, Zhou B, Davidson S, Yellon D, Riegler J, Price AN, Lythgoe MF, Pu WT, Riley PR., De novo cardiomyocytes from within the activated adult heart after injury. Nature 2011;474:640-644. doi: 10.1038/nature10188.
23. Zhou B, Honor LB, Ma Q, Oh JH, Lin RZ, Melero-Martin JM, von Gise A, Zhou P, Hu T, He L, Wu KH, Zhang H, Zhang Y, Pu WT., Thymosin beta 4 treatment after myocardial infarction does not reprogram epicardial cells into cardiomyocytes. J Mol Cell Cardiol 2012;52:43-47. doi: 10.1016/j.yjmcc.2011.08.020.
24. Ali SR, Hippenmeyer S, Saadat LV, Luo L, Weissman IL, Ardehali R., Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in mice. Proc Natl Acad Sci USA 2014;111:8850-8855. doi: 10.1073/pnas.1408233111.
25. Mollova M, Bersell K, Walsh S, Savla J, Das LT, Park SY, Silberstein LE, Dos Remedios CG, Graham D, Colan S, Kühn B., Cardiomyocyte proliferation contributes to heart growth in young humans. Proc Natl Acad Sci USA 2013;110:1446-1451. doi: 10.1073/pnas.1214608110.
26. Engel FB, Schebesta M, Keating MT., Anillin localization defect in cardiomyocyte binucleation. J Mol Cell Cardiol 2006;41:601-612. doi: 10.1016/j.yjmcc.2006.06.012.
27. Mahmoud AI, O'Meara CC, Gemberling M, Zhao L, Bryant DM, Zheng R, Gannon JB, Cai L, Choi WY, Egnaczyk GF, Burns CE, Burns CG, MacRae CA, Poss KD, Lee RT., Nerves regulate cardiomyocyte proliferation and heart regeneration. Dev Cell 2015;34:387-399. doi: 10.1016/j.devcel.2015.06.017.
28. Aguirre A, Montserrat N, Zacchigna S, In vivo activation of a conserved microRNA program induces mammalian heart regeneration. Cell Stem Cell 2014;15:589-604. doi: 10.1016/j.stem.2014.10.003.
29. Witman N, Murtuza B, Davis B, Arner A, Morrison JI., Recapitulation of developmental cardiogenesis governs the morphological and functional regeneration of adult newt hearts following injury. Dev Biol 2011;354:67-76. doi: 10.1016/j.ydbio.2011.03.021.
30. Poss KD, Wilson LG, Keating MT., Heart regeneration in zebrafish. Science 2002;298:2188-2190. doi: 10.1126/science.1077857.
31. Raya A, Koth CM, Büscher D, Kawakami Y, Itoh T, Raya RM, Sternik G, Tsai HJ, Rodríguez-Esteban C, Izpisuá-Belmonte JC., Activation of Notch signaling pathway precedes heart regeneration in zebrafish. Proc Natl Acad Sci USA 2003;100:suppl 1-11889 11895. doi: 10.1073/pnas.1834204100.
32. González-Rosa JM, Martín V, Peralta M, Torres M, Mercader N., Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish. Development 2011;138:1663-1674. doi: 10.1242/dev.060897.
33. Schnabel K, Wu CC, Kurth T, Weidinger G., Regeneration of cryoinjury induced necrotic heart lesions in zebrafish is associated with epicardial activation and cardiomyocyte proliferation. PLoS One 2011;6 e18503. doi: 10.1371/journal.pone.0018503.
34. Chablais F, Veit J, Rainer G, Jaźwińska A., The zebrafish heart regenerates after cryoinjury-induced myocardial infarction. BMC Dev Biol 2011:11-21. doi: 10.1186/1471-213X-11-21.
35. Wang J, Panáková D, Kikuchi K, Holdway JE, Gemberling M, Burris JS, Singh SP, Dickson AL, Lin YF, Sabeh MK, Werdich AA, Yelon D, Macrae CA, Poss KD., The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Development 2011;138:3421-3430. doi: 10.1242/dev.068601.
36. González-Rosa JM, Guzmán-Martínez G, Marques IJ, Sánchez-Iranzo H, Jiménez-Borreguero LJ, Mercader N., Use of echocardiography reveals reestablishment of ventricular pumping efficiency and partial ventricular wall motion recovery upon ventricular cryoinjury in the zebrafish. PLoS One 2014;9 e115604. doi: 10.1371/journal.pone.0115604.
37. Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, Sadek HA., Transient regenerative potential of the neonatal mouse heart. Science 2011:331-1078 1080. doi: 10.1126/science.1200708.
38. Porrello ER, Mahmoud AI, Simpson E, Johnson BA, Grinsfelder D, Canseco D, Mammen PP, Rothermel BA, Olson EN, Sadek HA., Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. Proc Natl Acad Sci USA 2013;110:187-192. doi: 10.1073/pnas.1208863110.
39. Jesty SA, Steffey MA, Lee FK, Breitbach M, Hesse M, Reining S, Lee JC, Doran RM, Nikitin AY, Fleischmann BK, Kotlikoff MI., c-kit+ precursors support postinfarction myogenesis in the neonatal, but not adult, heart. Proc Natl Acad Sci USA 2012;109:13380-13385. doi: 10.1073/pnas.1208114109.
40. Strungs EG, Ongstad EL, O'Quinn MP, Palatinus JA, Jourdan LJ, Gourdie RG., Cryoinjury models of the adult and neonatal mouse heart for studies of scarring and regeneration. Methods Mol Biol 2013;1037:343-353. doi: 10.1007/978-1-62703-505-7-20.
41. Itou J, Kawakami H, Burgoyne T, Kawakami Y., Life-long preservation of the regenerative capacity in the fin and heart in zebrafish. Biol Open 2012;1 739:746. doi: 10.1242/bio.20121057.
42. Kikuchi K, Poss KD., Cardiac regenerative capacity and mechanisms. Annu Rev Cell Dev Biol 2012-28 719 741. doi: 10.1146/annurev-cellbio-101011-155739.
43. Kikuchi K, Holdway JE, Major RJ, Blum N, Dahn RD, Begemann G, Poss KD., Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration. Dev Cell 2011;20:397-404. doi: 10.1016/j.devcel.2011.01.010.
44. Itou J, Oishi I, Kawakami H, Glass TJ, Richter J, Johnson A, Lund TC, Kawakami Y., Migration of cardiomyocytes is essential for heart regeneration in zebrafish. Development 2012;139:4133-4142. doi: 10.1242/dev.079756.
45. Lepilina A, Coon AN, Kikuchi K, Holdway JE, Roberts RW, Burns CG, Poss KD., A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Cell 2006;127:607-619. doi: 10.1016/j.cell.2006.08.052.
46. Kim J, Wu Q, Zhang Y, Wiens KM, Huang Y, Rubin N, Shimada H, Handin RI, Chao MY, Tuan TL, Starnes VA, Lien CL., PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts. Proc Natl Acad Sci USA 2010;107:17206-17210. doi: 10.1073/pnas.0915016107.
47. Jopling C, Sleep E, Raya M, Martí M, Raya A, Izpisuá Belmonte JC., Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 2010;464:606-609. doi: 10.1038/nature08899.
48. Kikuchi K, Holdway JE, Werdich AA, Anderson RM, Fang Y, Egnaczyk GF, Evans T, Macrae CA, Stainier DY, Poss KD., Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes. Nature 2010;464:601-605. doi: 10.1038/nature08804.
49. Wills AA, Holdway JE, Major RJ, Poss KD., Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish. Development 2008;135:183-192. doi: 10.1242/dev.010363.
50. Botting KJ, Wang KC, Padhee M, McMillen IC, Summers-Pearce B, Rattanatray L, Cutri N, Posterino GS, Brooks DA, Morrison JL., Early origins of heart disease: low birth weight and determinants of cardiomyocyte endowment. Clin Exp Pharmacol Physiol 2012;39:814-823. doi: 10.1111/j.1440-1681.2011.05649.x.
51. Bersell K, Arab S, Haring B, Kühn B., Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell 2009;138:257-270. doi: 10.1016/j.cell.2009.04.060.
52. Paradis AN, Gay MS, Zhang L., Binucleation of cardiomyocytes: the transition from a proliferative to a terminally differentiated state. Drug Discov Today 2014;19:602-609. doi: 10.1016/j.drudis.2013.10.019.
53. Raulf A, Horder H, Tarnawski L, Geisen C, Ottersbach A, Röll W, Jovinge S, Fleischmann BK, Hesse M., Transgenic systems for unequivocal identification of cardiac myocyte nuclei and analysis of cardiomyocyte cell cycle status. Basic Res Cardiol 2015;110:33. doi: 10.1007/s00395-015-0489-2.
54. Heallen T, Morikawa Y, Leach J, Tao G, Willerson JT, Johnson RL, Martin JF., Hippo signaling impedes adult heart regeneration. Development 2013-140 4683 4690. doi: 10.1242/dev.102798.
55. Jopling C, Suñe G, Morera C, Izpisua Belmonte JC., p38α MAPK regulates myocardial regeneration in zebrafish. Cell Cycle 2012;11:1195-1201. doi: 10.4161/cc.11.6.19637.
56. Jopling C, Suñé G, Faucherre A, Fabregat C, Izpisua Belmonte JC., Hypoxia induces myocardial regeneration in zebrafish. Circulation 2012;126:3017-3027. doi: 10.1161/CIRCULATIONAHA.112.107888.
57. Olson EN., MicroRNAs as therapeutic targets and biomarkers of cardiovascular disease. Sci Transl Med 2014;6 239ps3. doi: 10.1126/scitranslmed.3009008.
58. Eulalio A, Mano M, Dal Ferro M, Zentilin L, Sinagra G, Zacchigna S, Giacca M., Functional screening identifies miRNAs inducing cardiac regeneration. Nature 2012:492-376 381. doi: 10.1038/nature11739.
59. Yin VP, Lepilina A, Smith A, Poss KD., Regulation of zebrafish heart regeneration by miR-133. Dev Biol 2012;365:319-327. doi: 10.1016/j.ydbio.2012.02.018.
60. Tian Y, Liu Y, Wang T, A microrna-hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice. Sci Transl Med 2015;7 279ra238
61. Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE., Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 2011:8 376-388. doi: 10.1016/j.stem.2011.03.001.
62. Gemberling M, Karra R, Dickson AL, Poss KD., Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish. Elife 2015;4. doi: 10.7554/eLife.05871.
63. D'Uva G, Aharonov A, Lauriola M, ERBB2-triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nat Cell Biol 2015 17 627 638. doi: 10.1038/ncb3149.
64. Polizzotti BD, Ganapathy B, Walsh S, Choudhury S, Ammanamanchi N, Bennett DG, dos Remedios CG, Haubner BJ, Penninger JM, Kühn B., Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window. Sci Transl Med 2015;7 281ra45. doi: 10.1126/scitranslmed.aaa5171.
65. Kyritsis N, Kizil C, Zocher S, Kroehne V, Kaslin J, Freudenreich D, Iltzsche A, Brand M., Acute inflammation initiates the regenerative response in the adult zebrafish brain. Science 2012:338-1353 1356. doi: 10.1126/science.1228773.
66. Godwin JW, Pinto AR, Rosenthal NA., Macrophages are required for adult salamander limb regeneration. Proc Natl Acad Sci USA 2013;110:9415-9420. doi: 10.1073/pnas.1300290110.
67. Lavine KJ, Epelman S, Uchida K, Weber KJ, Nichols CG, Schilling JD, Ornitz DM, Randolph GJ, Mann DL., Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart. Proc Natl Acad Sci USA 2014;111:16029-16034. doi: 10.1073/pnas.1406508111.
68. Aurora AB, Porrello ER, Tan W, Mahmoud AI, Hill JA, Bassel-Duby R, Sadek HA, Olson EN., Macrophages are required for neonatal heart regeneration. J Clin Invest 2014;124:1382-1392. doi: 10.1172/JCI72181.
69. Takahashi K, Yamanaka S., Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663-676. doi: 10.1016/j.cell.2006.07.024.
70. Domian IJ, Chiravuri M, van der Meer P, Feinberg AW, Shi X, Shao Y, Wu SM, Parker KK, Chien KR., Generation of functional ventricular heart muscle from mouse ventricular progenitor cells. Science 2009;326:426-429. doi: 10.1126/science.1177350.
71. Lian X, Hsiao C, Wilson G, Zhu K, Hazeltine LB, Azarin SM, Raval KK, Zhang J, Kamp TJ, Palecek SP., Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci USA 2012;109:E1848-E1857. doi: 10.1073/pnas.1200250109.
72. Ueno S, Weidinger G, Osugi T, Kohn AD, Golob JL, Pabon L, Reinecke H, Moon RT, Murry CE., Biphasic role for Wnt/beta-catenin signaling in cardiac specification in zebrafish and embryonic stem cells. Proc Natl Acad Sci USA 2007;104:9685-9690. doi: 10.1073/pnas.0702859104.
73. Birket MJ, Ribeiro MC, Verkerk AO, Ward D, Leitoguinho AR, den Hartogh SC, Orlova VV, Devalla HD, Schwach V, Bellin M, Passier R, Mummery CL., Expansion and patterning of cardiovascular progenitors derived from human pluripotent stem cells. Nat Biotechnol 2015;33:970-979. doi: 10.1038/nbt.3271.
74. Papadaki M, Bursac N, Langer R, Merok J, Vunjak-Novakovic G, Freed LE., Tissue engineering of functional cardiac muscle: molecular, structural, and electrophysiological studies. Am J Physiol Heart Circ Physiol 2001;280:H168-H178
75. Lesman A, Habib M, Caspi O, Gepstein A, Arbel G, Levenberg S, Gepstein L., Transplantation of a tissue-engineered human vascularized cardiac muscle. Tissue Eng Part A 2010;16:115-125. doi: 10.1089/ten.TEA.2009.0130.
76. Caspi O, Lesman A, Basevitch Y, Gepstein A, Arbel G, Habib IH, Gepstein L, Levenberg S., Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circ Res 2007;100:263-272. doi: 10.1161/01.RES.0000257776.05673.ff.
77. Chong JJ, Yang X, Don CW, Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 2014;510:273-277. doi: 10.1038/nature13233.
78. Weintraub H, Tapscott SJ, Davis RL, Thayer MJ, Adam MA, Lassar AB, Miller AD., Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci USA 1989;86:5434-5438
79. Choi J, Costa ML, Mermelstein CS, Chagas C, Holtzer S, Holtzer H., MyoD converts primary dermal fibroblasts, chondroblasts, smooth muscle, and retinal pigmented epithelial cells into striated mononucleated myoblasts and multinucleated myotubes. Proc Natl Acad Sci USA 1990;87:7988-7992
80. Davis RL, Weintraub H, Lassar AB., Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 1987;51:987-1000
81. Sancho-Martinez I, Baek SH, Izpisua Belmonte JC., Lineage conversion methodologies meet the reprogramming toolbox. Nat Cell Biol 2012;14:892-899. doi: 10.1038/ncb2567.
82. Vierbuchen T, Wernig M., Direct lineage conversions: unnatural but useful? Nat Biotechnol 2011;29:892-907. doi: 10.1038/nbt.1946.
83. He Q, Trindade PT, Stumm M, Li J, Zammaretti P, Bettiol E, Dubois-Dauphin M, Herrmann F, Kalangos A, Morel D, Jaconi ME., Fate of undifferentiated mouse embryonic stem cells within the rat heart: role of myocardial infarction and immune suppression. J Cell Mol Med 2009;13:188-201. doi: 10.1111/j.1582-4934.2008.00323.x.
84. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D., Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 2010;142:375-386. doi: 10.1016/j.cell.2010.07.002.
85. Chen JX, Krane M, Deutsch MA, Wang L, Rav-Acha M, Gregoire S, Engels MC, Rajarajan K, Karra R, Abel ED, Wu JC, Milan D, Wu SM., Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5. Circ Res 2012;111:50-55. doi: 10.1161/CIRCRESAHA.112.270264.
86. Song K, Nam YJ, Luo X, Qi X, Tan W, Huang GN, Acharya A, Smith CL, Tallquist MD, Neilson EG, Hill JA, Bassel-Duby R, Olson EN., Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature 2012;485:599-604. doi: 10.1038/nature11139.
87. Protze S, Khattak S, Poulet C, Lindemann D, Tanaka EM, Ravens U., A new approach to transcription factor screening for reprogramming of fibroblasts to cardiomyocyte-like cells. J Mol Cell Cardiol 2012;53:323-332. doi: 10.1016/j.yjmcc.2012.04.010.
88. Jayawardena TM, Egemnazarov B, Finch EA, Zhang L, Payne JA, Pandya K, Zhang Z, Rosenberg P, Mirotsou M, Dzau VJ., MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res 2012;110:1465-1473. doi: 10.1161/CIRCRESAHA.112.269035.
89. Inagawa K, Miyamoto K, Yamakawa H, Muraoka N, Sadahiro T, Umei T, Wada R, Katsumata Y, Kaneda R, Nakade K, Kurihara C, Obata Y, Miyake K, Fukuda K, Ieda M., Induction of cardiomyocyte-like cells in infarct hearts by gene transfer of Gata4, Mef2c, and Tbx5. Circ Res 2012;111:1147-1156. doi: 10.1161/CIRCRESAHA.112.271148.
90. Islas JF, Liu Y, Weng KC, Robertson MJ, Zhang S, Prejusa A, Harger J, Tikhomirova D, Chopra M, Iyer D, Mercola M, Oshima RG, Willerson JT, Potaman VN, Schwartz RJ., Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors. Proc Natl Acad Sci USA 2012;109:13016-13021. doi: 10.1073/pnas.1120299109.
91. Nam YJ, Song K, Luo X, Daniel E, Lambeth K, West K, Hill JA, DiMaio JM, Baker LA, Bassel-Duby R, Olson EN., Reprogramming of human fibroblasts toward a cardiac fate. Proc Natl Acad Sci USA 2013;110:5588-5593. doi: 10.1073/pnas.1301019110.
92. Wada R, Muraoka N, Inagawa K, Induction of human cardiomyocyte-like cells from fibroblasts by defined factors. Proc Natl Acad Sci USA 2013;110:12667-12672. doi: 10.1073/pnas.1304053110.
93. Fu JD, Stone NR, Liu L, Spencer CI, Qian L, Hayashi Y, Delgado-Olguin P, Ding S, Bruneau BG, Srivastava D., Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state. Stem Cell Reports 2013;1 235:247. doi: 10.1016/j.stemcr.2013.07.005.
94. Sadahiro T, Yamanaka S, Ieda M., Direct cardiac reprogramming: progress and challenges in basic biology and clinical applications. Circ Res 2015-116 1378 1391. doi: 10.1161/CIRCRESAHA.116.305374.
95. Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, Conway SJ, Fu JD, Srivastava D., In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 2012;485:593-598. doi: 10.1038/nature11044.
96. Kubo H, Shimizu T, Yamato M, Fujimoto T, Okano T., Creation of myocardial tubes using cardiomyocyte sheets and an in vitro cell sheet-wrapping device. Biomaterials 2007;28:3508-3516. doi: 10.1016/j.biomaterials.2007.04.016.
97. Sekine H, Shimizu T, Yang J, Kobayashi E, Okano T., Pulsatile myocardial tubes fabricated with cell sheet engineering. Circulation 2006;114:I87-I93. doi: 10.1161/CIRCULATIONAHA.105.000273.
98. Stevens KR, Kreutziger KL, Dupras SK, Korte FS, Regnier M, Muskheli V, Nourse MB, Bendixen K, Reinecke H, Murry CE., Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue. Proc Natl Acad Sci USA 2009;106:16568-16573. doi: 10.1073/pnas.0908381106.
99. Wei K, Serpooshan V, Hurtado C, Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature 2015;525:479-485. doi: 10.1038/nature15372.
100. Li M, Suzuki K, Kim NY, Liu GH, Izpisua Belmonte JC., A cut above the rest: targeted genome editing technologies in human pluripotent stem cells. J Biol Chem 2014;289:4594-4599. doi: 10.1074/jbc.R113.488247.
101. Wu J, Izpisua Belmonte JC., Dynamic pluripotent stem cell states and their applications. Cell Stem Cell 2015;17:509-525. doi: 10.1016/j.stem.2015.10.009.