Direct reprogramming of fibroblasts into cardiomyocytes for cardiac regenerative medicine

Circulation Journal

Volumn 79, Issue 2, 2015, Pages 245-254

  Fu, Ji Dong ^a,b,c   Srivastava, Deepak ^b,c,d  

^a CASE WESTERN RESERVE UNIVERSITY   (United States)

^b GLADSTONE INSTITUTE OF CARDIOVASCULAR DISEASE   (United States)

^c Roddenberry Center for Stem Cell Biology and Medicine at Gladstone   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cardiomyocytes; Epigenetic reprogramming; Heart failure; Regenerative medicine

Indexed keywords

BETA1 INTEGRIN; BONE MORPHOGENETIC PROTEIN; CALVASCULIN; ENHANCED GREEN FLUORESCENT PROTEIN; FIBROBLAST GROWTH FACTOR; FIBRONECTIN; HEPARIN BINDING EPIDERMAL GROWTH FACTOR; INTERLEUKIN 6; LENTIVIRUS VECTOR; MICRORNA; MICRORNA 1; MICRORNA 133; MICRORNA 208; MICRORNA 499; MYOCARDIN; MYOCYTE ENHANCER FACTOR 2; MYOD PROTEIN; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR GATA; TRANSCRIPTION FACTOR GATA 4; TRANSCRIPTION FACTOR NKX2.5; TRANSCRIPTION FACTOR RUNX2; TRANSCRIPTION FACTOR TBX5; TRANSCRIPTOME; TRANSFORMING GROWTH FACTOR BETA; TROPONIN T; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULOTROPIN;

ARTICLE; CELL FATE; CELL INTERACTION; CELL TRANSDIFFERENTIATION; FIBROBLAST; FLUORESCENCE ACTIVATED CELL SORTING; GENE EXPRESSION; HEART DEVELOPMENT; HEART FAILURE; HEART FUNCTION; HEART INFARCTION; HEART MUSCLE CELL; HUMAN; IMMUNE RESPONSE; INFLAMMATION; NUCLEAR REPROGRAMMING; POLYMERASE CHAIN REACTION; REGENERATIVE MEDICINE; ANIMAL; METABOLISM; MOUSE; MYOCARDIAL INFARCTION; PROCEDURES; RAT;

ANIMALS; CELLULAR REPROGRAMMING; FIBROBLASTS; HUMANS; MICE; MYOCARDIAL INFARCTION; MYOCYTES, CARDIAC; RATS; REGENERATIVE MEDICINE;

EID: 84928266885     PISSN: 13469843     EISSN: 13474820     Source Type: Journal    
DOI: 10.1253/circj.CJ-14-1372     Document Type: Article

References (79)

1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Executive summary: Heart disease and stroke statistics--2014 update: A report from the American Heart Association. Circulation 2014; 129: 399–410.
2. Kikuchi K, Poss KD. Cardiac regenerative capacity and mechanisms. Annu Rev Cell Dev Biol 2012; 28: 719–741.
3. Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 1962; 10: 622–640.
4. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663–676.
5. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 2010; 142: 375–386.
6. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 2010; 463: 1035–1041.
7. Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, et al. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 2011; 475: 386–389.
8. Szabo E, Rampalli S, Risueno RM, Schnerch A, Mitchell R, Fiebig-Comyn A, et al. Direct conversion of human fibroblasts to multilineage blood progenitors. Nature 2010; 468: 521–526.
9. Margariti A, Winkler B, Karamariti E, Zampetaki A, Tsai TN, Baban D, et al. Direct reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelialization in tissue-engineered vessels. Proc Natl Acad Sci USA 2012; 109: 13793–13798.
10. Snider P, Standley KN, Wang J, Azhar M, Doetschman T, Conway SJ. Origin of cardiac fibroblasts and the role of periostin. Circ Res 2009; 105: 934–947.
11. Jayawardena TM, Egemnazarov B, Finch EA, Zhang L, Payne JA, Pandya K, et al. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res 2012; 110: 1465–1473.
12. 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.
13. Song K, Nam YJ, Luo X, Qi X, Tan W, Huang GN, et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature 2012; 485: 599–604.
14. Addis RC, Ifkovits JL, Pinto F, Kellam LD, Esteso P, Rentschler S, et al. Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success. J Mol Cell Cardiol 2013; 60: 97–106.
15. Christoforou N, Chellappan M, Adler AF, Kirkton RD, Wu T, Addis RC, 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 2013; 8: e63577, doi:10.1371/journal.pone.0063577.
16. Fu JD, Stone NR, Liu L, Spencer CI, Qian L, Hayashi Y, et al. Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state. Stem Cell Rep 2013; 1: 235–247.
17. Nam YJ, Song K, Luo X, Daniel E, Lambeth K, West K, et al. Reprogramming of human fibroblasts toward a cardiac fate. Proc Natl Acad Sci USA 2013; 110: 5588–5593.
18. Wada R, Muraoka N, Inagawa K, Yamakawa H, Miyamoto K, Sadahiro T, et al. Induction of human cardiomyocyte-like cells from fibroblasts by defined factors. Proc Natl Acad Sci USA 2013; 110: 12667–12672.
19. Yi BA, Mummery CL, Chien KR. Direct cardiomyocyte reprogramming: A new direction for cardiovascular regenerative medicine. Cold Spring Harbor Perspect Med 2013; 3: a014050.
20. Srivastava D, Berry EC. Cardiac reprogramming: From mouse toward man. Curr Opin Genet Dev 2013; 23: 574–578.
21. Qian L, Srivastava D. Direct cardiac reprogramming: From developmental biology to cardiac regeneration. Circ Res 2013; 113: 915–921.
22. Nam YJ, Song K, Olson EN. Heart repair by cardiac reprogramming. Nat Med 2013; 19: 413–415.
23. Addis RC, Epstein JA. Induced regeneration: The progress and promise of direct reprogramming for heart repair. Nat Med 2013; 19: 829–836.
24. Muraoka N, Ieda M. Direct reprogramming of fibroblasts into myocytes to reverse fibrosis. Annu Rev Physiol 2014; 76: 21–37.
25. Srivastava D. Genetic regulation of cardiogenesis and congenital heart disease. Annu Rev Pathol 2006; 1: 199–213.
26. Rana MS, Christoffels VM, Moorman AF. A molecular and genetic outline of cardiac morphogenesis. Acta Physiol 2013; 207: 588–615.
27. Srivastava D. Making or breaking the heart: From lineage determination to morphogenesis. Cell 2006; 126: 1037–1048.
28. Huang J, Elicker J, Bowens N, Liu X, Cheng L, Cappola TP, et al. Myocardin regulates BMP10 expression and is required for heart development. J Clin Invest 2012; 122: 3678–3691.
29. Ivey KN, Srivastava D. MicroRNAs as regulators of differentiation and cell fate decisions. Cell Stem Cell 2010; 7: 36–41.
30. Cordes KR, Srivastava D. MicroRNA regulation of cardiovascular development. Circ Res 2009; 104: 724–732.
31. Malizia AP, Wang DZ. MicroRNAs in cardiomyocyte development. Wiley Interdiscip Rev Syst Biol Med 2011; 3: 183–190.
32. Heidersbach A, Saxby C, Carver-Moore K, Huang Y, Ang YS, de Jong PJ, et al. MicroRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart. eLife 2013; 2: e01323, doi:10.7554/eLife.01323.
33. Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M, Muth AN, et al. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 2007; 129: 303–317.
34. Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 2005; 436: 214–220.
35. Kwon C, Han Z, Olson EN, Srivastava D. MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci USA 2005; 102: 18986–18991.
36. Ivey KN, Muth A, Arnold J, King FW, Yeh RF, Fish JE, et al. MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell 2008; 2: 219–229.
37. Fu JD, Rushing SN, Lieu DK, Chan CW, Kong CW, Geng L, et al. Distinct roles of microRNA-1 and -499 in ventricular specification and functional maturation of human embryonic stem cell-derived cardiomyocytes. PloS One 2011; 6: e27417, doi:10.1371/journal.pone.0027417.
38. Shieh JT, Huang Y, Gilmore J, Srivastava D. Elevated miR-499 levels blunt the cardiac stress response. PloS One 2011; 6: e19481, doi:10.1371/journal.pone.0019481.
39. Jelaska A, Strehlow D, Korn JH. Fibroblast heterogeneity in physiological conditions and fibrotic disease. Springer Semin Immunopathol 1999; 21: 385–395.
40. Lekic PC, Pender N, McCulloch CA. Is fibroblast heterogeneity relevant to the health, diseases, and treatments of periodontal tissues? Crit Rev Oral Biol Med 1997; 8: 253–268.
41. Chang HY, Chi JT, Dudoit S, Bondre C, van de Rijn M, Botstein D, et al. Diversity, topographic differentiation, and positional memory in human fibroblasts. Proc Natl Acad Sci USA 2002; 99: 12877–12882.
42. Souders CA, Bowers SL, Baudino TA. Cardiac fibroblast: The renaissance cell. Circ Res 2009; 105: 1164–1176.
43. Krenning G, Zeisberg EM, Kalluri R. The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol 2010; 225: 631–637.
44. Goldsmith EC, Hoffman A, Morales MO, Potts JD, Price RL, McFadden A, et al. Organization of fibroblasts in the heart. Dev Dynam 2004; 230: 787–794.
45. Hudon-David F, Bouzeghrane F, Couture P, Thibault G. Thy-1 expression by cardiac fibroblasts: Lack of association with myofibroblast contractile markers. J Mol Cell Cardiol 2007; 42: 991–1000.
46. Strutz F, Okada H, Lo CW, Danoff T, Carone RL, Tomaszewski JE, et al. Identification and characterization of a fibroblast marker: FSP1. J Cell Biol 1995; 130: 393–405.
47. Ieda M, Tsuchihashi T, Ivey KN, Ross RS, Hong TT, Shaw RM, et al. Cardiac fibroblasts regulate myocardial proliferation through beta1 integrin signaling. Dev Cell 2009; 16: 233–244.
48. Chilton L, Giles WR, Smith GL. Evidence of intercellular coupling between co-cultured adult rabbit ventricular myocytes and myofibroblasts. J Physiol 2007; 583: 225–236.
49. Baudino TA, McFadden A, Fix C, Hastings J, Price R, Borg TK. Cell patterning: Interaction of cardiac myocytes and fibroblasts in three-dimensional culture. Microscopy Microanal 2008; 14: 117–125.
50. Shinde AV, Frangogiannis NG. Fibroblasts in myocardial infarction: A role in infammation and repair. J Mol Cell Cardiol 2014; 70: 74–82.
51. Brown RD, Ambler SK, Mitchell MD, Long CS. The cardiac fibroblast: Therapeutic target in myocardial remodeling and failure. Annu Rev Pharmacol Toxicol 2005; 45: 657–687.
52. Frangogiannis NG. The infammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol 2014; 11: 255–265.
53. Blau HM, Pavlath GK, Hardeman EC, Chiu CP, Silberstein L, Webster SG, et al. Plasticity of the differentiated state. Science 1985; 230: 758–766.
54. Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 1987; 51: 987–1000.
55. Weintraub H, Tapscott SJ, Davis RL, Thayer MJ, Adam MA, Lassar AB, et al. 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.
56. Kim TK, Sul JY, Peternko NB, Lee JH, Lee M, Patel VV, et al. Transcriptome transfer provides a model for understanding the phenotype of cardiomyocytes. Proc Natl Acad Sci USA 2011; 108: 11918–11923.
57. Chien KR, Yi BA, Xu H, Mummery CL. Cardiomyocyte reprogramming and the new age of cellular alchemy. J Mol Cell Cardiol 2012; 53: 311–313.
58. Ifkovits JL, Addis RC, Epstein JA, Gearhart JD. Inhibition of TGFβ signaling increases direct conversion of fibroblasts to induced car-diomyocytes. PloS One 2014; 9: e89678, doi:10.1371/journal.pone.0089678.
59. Liu N, Bezprozvannaya S, Williams AH, Qi X, Richardson JA, Bassel-Duby R, et al. MicroRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Gene Dev 2008; 22: 3242–3254.
60. Callis TE, Pandya K, Seok HY, Tang RH, Tatsuguchi M, Huang ZP, et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest 2009; 119: 2772–2786.
61. Muraoka N, Yamakawa H, Miyamoto K, Sadahiro T, Umei T, Isomi M, et al. Mir-133 promotes cardiac reprogramming by directly repressing Snail and silencing fibroblast signatures. EMBO J 2014; 33: 1565–1581.
62. Takeuchi JK, Bruneau BG. Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 2009; 459: 708–711.
63. Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 2012; 485: 593–598.
64. Bieniasz PD, Weiss RA, McClure MO. Cell cycle dependence of foamy retrovirus infection. J Virol 1995; 69: 7295–7299.
65. Zebrowski DC, Engel FB. The cardiomyocyte cell cycle in hypertrophy, tissue homeostasis, and regeneration. Rev Physiol Biochem Pharmacol 2013; 165: 67–96.
66. Inagawa K, Miyamoto K, Yamakawa H, Muraoka N, Sadahiro T, Umei T, et al. Induction of cardiomyocyte-like cells in infarct hearts by gene transfer of Gata4, Mef2c, and Tbx5. Circ Res 2012; 111: 1147–1156.
67. Jayawardena TM, Finch EA, Zhang L, Zhang H, Hodgkinson C, Pratt RE, et al. MicroRNA induced cardiac reprogramming in vivo: Evidence for mature cardiac myocytes and improved cardiac function. Circ Res 2014 October 28, doi:10.1161/CIRCRESAHA.116.304510.
68. Srivastava D, Ieda M, Fu J, Qian L. Cardiac repair with thymosin β4 and cardiac reprogramming factors. Ann NY Acad Sci 2012; 1270: 66–72.
69. Bock-Marquette I, Saxena A, White MD, Dimaio JM, Srivastava D. Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature 2004; 432: 466–472.
70. Mathison M, Gersch RP, Nasser A, Lilo S, Korman M, Fourman 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 2012; 1: e005652, doi:10.1161/JAHA.112.005652.
71. Chen JX, Krane M, Deutsch MA, Wang L, Rav-Acha M, Gregoire S, et al. Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5. Circ Res 2012; 111: 50–55.
72. Wang L, Liu Z, Yin C, Asfour H, Chen OM, Li Y, et al. Stoichiometry of Gata4, Mef2c, and Tbx5 influences the efficiency and quality of induced cardiac myocyte reprogramming. Circ Res 2014 November 21, doi:10.1161/CIRCRESAHA.116.305547.
73. Qian L, Berry EC, Fu JD, Ieda M, Srivastava D. Reprogramming of mouse fibroblasts into cardiomyocyte-like cells in vitro. Nat Protocol 2013; 8: 1204–1215.
74. Srivastava D, Ieda M. Critical factors for cardiac reprogramming. Circ Res 2012; 111: 5–8.
75. Bird SD, Doevendans PA, van Rooijen MA, Brutel de la Riviere A, Hassink RJ, Passier R, et al. The human adult cardiomyocyte phenotype. Cardiovasc Res 2003; 58: 423–434.
76. Tian Y, Morrisey EE. Importance of myocyte-nonmyocyte interactions in cardiac development and disease. Circ Res 2012; 110: 1023–1034.
77. Hsieh PC, Davis ME, Lisowski LK, Lee RT. Endothelial-cardiomyocyte interactions in cardiac development and repair. Annu Rev Physiol 2006; 68: 51–66.
78. Aurora AB, Porrello ER, Tan W, Mahmoud AI, Hill JA, Bassel-Duby R, et al. Macrophages are required for neonatal heart regeneration. J Clin Invest 2014; 124: 1382–1392.
79. Hirai H, Katoku-Kikyo N, Keirstead SA, Kikyo N. Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the myod transactivation domain. Cardiovasc Res 2013; 100: 105–113.