Navigating the labyrinth of cardiac regeneration

Developmental Dynamics

Volumn 245, Issue 7, 2016, Pages 751-761

  Lambers, Erin ^a   Kume, Tsutomu ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

adult stem cells; cardiomyogenesis; direct lineage conversion; directed differentiation; heart development; reprogramming

Indexed keywords

ADULT STEM CELL; CARDIAC MUSCLE CELL; CARDIAC REGENERATION; CARDIOVASCULAR MORTALITY; CELL DIFFERENTIATION; CELL LINEAGE; CLINICAL TRIAL (TOPIC); DIFFERENTIATION; HEALTH CARE SYSTEM; HEART DEVELOPMENT; HEART INFARCTION; HUMAN; HYPERTENSION; MORBIDITY; NONHUMAN; PRIORITY JOURNAL; REVIEW; STEM CELL TRANSPLANTATION; TISSUE REGENERATION;

EID: 84975143309     PISSN: 10588388     EISSN: 10970177     Source Type: Journal    
DOI: 10.1002/dvdy.24397     Document Type: Review

References (120)

1. Abdul Kadir SHS, Ali NN, Mioulane M, Brito-Martins M, Abu-Hayyeh S, Foldes G, Moshkov AV, Williamson C, Harding SE, Gorelik J. 2009. Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease. J Cell Mol Med 13:3730–3741.
2. Acharya A, Baek ST, Huang G, Eskiocak B, Goetsch S, Sung CY, Banfi S, Sauer MF, Olsen GS, Duffield JS, Olson EN, Tallquist MD. 2012. The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors. Development 139:2139–2149.
3. Alfaro MP, Young PP. 2012. Lessons from genetically altered mesenchymal stem cells (MSCs): candidates for improved MSC-directed myocardial repair. Cell Transplant 21:1065–1074.
4. Assmus B, Fischer-Rasokat U, Honold J, Seeger FH, Fichtlscherer S, Tonn T, Seifried E, Schächinger V, Dimmeler S, Zeiher AM, TOPCARE-CHD Registry. 2007. Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure: results of the TOPCARE-CHD Registry. Circ Res 100:1234–1241.
5. Bakker ML, Boink GJJ, Boukens BJ, Verkerk AO, van den Boogaard M, den Haan AD, Hoogaars WMH, Buermans HP, de Bakker JMT, Seppen J, Tan HL, Moorman AFM, 't Hoen PAC, Christoffels VM. 2012. T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into pacemaker-like cells. Cardiovasc Res 94:439–449.
6. Bartunek J, Behfar A, Dolatabadi D, Vanderheyden M, Ostojic M, Dens J, El Nakadi B, Banovic M, Beleslin B, Vrolix M, Legrand V, Vrints C, Vanoverschelde JL, Crespo-Diaz R, Homsy C, Tendera M, Waldman S, Wijns W, Terzic A. 2013. Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics. J Am Coll Cardiol 61:2329–2338.
7. Bearzi C, Rota M, Hosoda T, Tillmanns J, Nascirnbene A, De Angelis A, Yasuzawa-Amano S, Trofimova I, Siggins RW, LeCapitaine N, Cascapera S, Beltrami AP, D'Alessandro DA, Zias E, Quaini F, Urbanek K, Michler RE, Bolli R, Kajstura J, Leri A, Anversa P. 2007. Human cardiac stem cells. Proc Natl Acad Sci U S A 104:14068–14073.
8. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B, Anversa P. 2003. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776.
9. 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. 2009. Evidence for cardiomyocyte renewal in humans. Science 324:98–102.
10. Bolli R, Jneid H, Tang X-L, Dawn B, Rimoldi O, Mosna F, Loredo M, Gatti A, Kajstura J, Leri A, Bearzi C, Abdel-Latif A, Anversa P. 2006. Intracoronary administration of cardiac stem cells improves cardiac function in pigs with old infarction. Circulation 114:239–239.
11. Bolli R, Chugh AR, D'Amario D, Loughran JH, Stoddard MF, Ikram S, Beache GM, Wagner SG, Leri A, Hosoda T, Sanada F, Elmore JB, Goichberg P, Cappetta D, Solankhi NK, Fahsah I, Rokosh DG, Slaughter MS, Kajstura J, Anversa P. 2011. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 378:1847–1857.
12. Braitsch CM, Combs MD, Quaggin SE, Yutzey KE. 2012. Pod1/Tcf21 is regulated by retinoic acid signaling and inhibits differentiation of epicardium-derived cells into smooth muscle in the developing heart. Dev Biol 368:345–357.
13. Buckingham M, Meilhac S, Zaffran S. 2005. Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet 6:826–835.
14. Cai C-L, Liang X, Shi Y, Chu P-H, Pfaff SL, Chen J, Evans S. 2003. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell 5:877–889.
15. Caxaria S, Arthold S, Nathwani AC, Goh PA. 2016. Generation of Integration-Free Patient Specific iPS cells using episomal plasmids under feeder free conditions. Methods Mol Biol 1353:355–366.
16. Chong JJH, Yang X, Don CW, Minami E, Liu Y-W, Weyers JJ, Mahoney WM, Van Biber B, Cook SM, Palpant NJ, Gantz JA, Fugate JA, Muskheli V, Gough GM, Vogel KW, Astley CA, Hotchkiss CE, Baldessari A, Pabon L, Reinecke H, Gill EA, Nelson V, Kiem H-P, Laflamme MA, Murry CE. 2014. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510:273–277.
17. Cleland JGF, Coletta AP, Abdellah AT, Nasir M, Hobson N, Freemantle N, Clark AL. 2007. Clinical trials update from the American Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty. Eur J Heart Fail 9:92–97.
18. Combs MD, Braitsch CM, Lange AW, James JF, Yutzey KE. 2011. NFATC1 promotes epicardium-derived cell invasion into myocardium. Development 138:1747–1757.
19. Davis RL, Weintraub H, Lassar AB. 1987. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51:987–1000.
20. Dawn B, Stein AB, Urbanek K, Rota M, Whang B, Rastaldo R, Torella D, Tang XL, Rezazadeh A, Kajstura J, Leri A, Hunt G, Varma J, Prabhu SD, Anversa P, Bolli R. 2005. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci U S A 102:3766–3771.
21. de Boer BA, van den Berg G, de Boer PAJ, Moorman AFM, Ruijter JM. 2012. Growth of the developing mouse heart: an interactive qualitative and quantitative 3D atlas. Dev Biol 368:203–213.
22. Dellefave LM, Pytel P, Mewborn S, Mora B, Guris DL, Fedson S, Waggoner D, Moskowitz I, McNally EM. 2009. Sarcomere mutations in cardiomyopathy with left ventricular hypertrabeculation. Circ Cardiovasc Genet 2:442–449.
23. Dodou E, Verzi MP, Anderson JP, Xu S-M, Black BL. 2004. Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development. Development 131:3931–3942.
24. Dubois NC, Craft AM, Sharma P, Elliott DA, Stanley EG, Elefanty AG, Gramolini A, Keller G. 2011. SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells. Nat Biotechnol 29:1011–1018.
25. Finegold JA, Asaria P, Francis DP. 2013. Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations. Int J Cardiol 168:934–945.
26. Fischer KM, Cottage CT, Wu W, Din S, Gude NA, Avitabile D, Quijada P, Collins BL, Fransioli J, Sussman MA. 2009. Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase. Circulation 120:2077–2087.
27. GBD 2013 Mortality and Causes of Death Collaborators. 2015. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385:117–171.
28. Gittenberger-de Groot AC, Vrancken Peeters MP, Mentink MM, Gourdie RG, Poelmann RE. 1998. Epicardium-derived cells contribute a novel population to the myocardial wall and the atrioventricular cushions. Circ Res 82:1043–1052.
29. Gould RA, Aboulmouna LM, Varner JD, Butcher JT. 2013. Hierarchical approaches for systems modeling in cardiac development. Wiley Interdiscip Rev Syst Biol Med 5:289–305.
30. Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, Brinker JA, Breton E, Davis-Sproul J, Schulman IH, Byrnes J, Mendizabal AM, Lowery MH, Rouy D, Altman P, Wong Po Foo C, Ruiz P, Amador A, Da Silva J, McNiece IK, Heldman AW, George R, Lardo A. 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.
31. Hattori F, Chen H, Yamashita H, Tohyama S, Satoh Y-S, Yuasa S, Li W, Yamakawa H, Tanaka T, Onitsuka T, Shimoji K, Ohno Y, Egashira T, Kaneda R, Murata M, Hidaka K, Morisaki T, Sasaki E, Suzuki T, Sano M, Makino S, Oikawa S, Fukuda K. 2010. Nongenetic method for purifying stem cell-derived cardiomyocytes. Nat Methods 7:61–66.
32. Heikinheimo M, Scandrett JM, Wilson DB, 1994. Localization of transcription factor GATA-4 to regions of the mouse embryo involved in cardiac development. Dev Biol 164:361–373.
33. Hosoda T, D'Amario D, Cabral-da-Silva MC, Zheng H, Padin-Iruegas ME, Ogorek B, Ferreira-Martins J, Yasuzawa-Amano S, Amano K, Ide-Iwata N, Cheng W, Rota M, Urbanek K, Kajstura J, Anversa P, Leri A. 2009. Clonality of mouse and human cardiomyogenesis in vivo. Proc Natl Acad Sci U S A 106:17169–17174.
34. Houtgraaf JH, den Dekker WK, van Dalen BM, Springeling T, de Jong R, van Geuns RJ, Geleijnse ML, Fernandez-Aviles F, Zijlsta F, Serruys PW, Duckers HJ. 2012. First experience in humans using adipose tissue–derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 59:539–540.
35. Hsieh PCH, Segers VFM, Davis ME, MacGillivray C, Gannon J, Molkentin JD, Robbins J, Lee RT. 2007. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med 13:970–974.
36. Hu Y-F, Dawkins JF, Cho HC, Marbán E, Cingolani E. 2014. Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block. Sci Transl Med 6:245ra94.
37. Itzhaki I, Maizels L, Huber I, Zwi-Dantsis L, Caspi O, Winterstern A, Feldman O, Gepstein A, Arbel G, Hammerman H, Boulos M, Gepstein L. 2011. Modelling the long QT syndrome with induced pluripotent stem cells. Nature 471:225–229.
38. 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.
39. Jesty SA, Steffey MA, Lee FK, Breitbach M, Hesse M, Reining S, Lee JC, Doran RM, Nikitin AY, Fleischmann BK, Kotlikoff MI. 2012. c-kit+ precursors support postinfarction myogenesis in the neonatal, but not adult, heart. Proc Natl Acad Sci U S A 109:13380–13385.
40. Kaltenbrun E, Tandon P, Amin NM, Waldron L, Showell C, Conlon FL. 2011. Xenopus: an emerging model for studying congenital heart disease. Birth Defect Res A Clin Mol Teratol 91:495–510.
41. Kapoor N, Liang W, Marbán E, Cho HC. 2013. Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18. Nat Biotechnol 31:54–62.
42. 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.
43. Kirschner KM, Wagner N, Wagner K-D, Wellmann S, Scholz H. 2006. The Wilms tumor suppressor Wt1 promotes cell adhesion through transcriptional activation of the alpha4integrin gene. J Biol Chem 281:31930–31939.
44. Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, Reinecke H, Xu C, Hassanipour M, Police S, O'Sullivan C, Collins L, Chen Y, Minami E, Gill EA, Ueno S, Yuan C, Gold J, Murry CE. 2007. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25:1015–1024.
45. Lahti AL, Kujala VJ, Chapman H, Koivisto A-P, Pekkanen-Mattila M, Kerkelä E, Hyttinen J, Kontula K, Swan H, Conklin BR, Yamanaka S, Silvennoinen O, Aalto-Setälä K. 2012. Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture. Dis Model Mech 5:220–230.
46. 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 U S A 109:E1848–E1857.
47. Lieu DK, Liu J, Siu C-W, McNerney GP, Tse H-F, Abu-Khalil A, Huser T, Li RA. 2009. Absence of transverse tubules contributes to non-uniform Ca(2+) wavefronts in mouse and human embryonic stem cell-derived cardiomyocytes. Stem Cells Dev 18:1493–1500.
48. Liu J, Stainier DYR. 2012. Zebrafish in the study of early cardiac development. Circ Res 110:870–874.
49. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, de Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J, American Heart Association Statistics Committee and Stroke Statistics Subcommittee. 2010. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 121:948–954.
50. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grøgaard HK, Bjørnerheim R, Brekke M, Müller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K. 2006. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 355:1199–1209.
51. Ma Q, Zhou B, Pu WT. 2008. Reassessment of Isl1 and Nkx2-5 cardiac fate maps using a Gata4-based reporter of Cre activity. Dev Biol 323:98–104.
52. Mahmoud AI, Kocabas F, Muralidhar SA, Kimura W, Koura AS, Thet S, Porrello ER, Sadek HA. 2013. Meis1 regulates postnatal cardiomyocyte cell cycle arrest. Nature 497:249–253.
53. Mahmoud AI, O'Meara CC, Gemberling M, Zhao L, Bryant DM, Zheng R, Gannon JB, Cai L, Choi W-Y, Egnaczyk GF, Burns CE, Burns CG, Macrae CA, Poss KD, Lee RT. 2015. Nerves regulate cardiomyocyte proliferation and heart regeneration. Dev Cell 34:387–399.
54. Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LEJ, Berman D, Czer LSC, Marbán L, Mendizabal A, Johnston PV, Russell SD, Schuleri KH, Lardo AC, Gerstenblith G, Marbán E. 2012. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 379:895–904.
55. Malliaras K, Makkar RR, Smith RR, Cheng K, Wu E, Bonow RO, Marbán L, Mendizabal A, Cingolani E, Johnston PV, Gerstenblith G, Schuleri KH, Lardo AC, Marbán E. 2014. Intracoronary cardiosphere-derived cells after myocardial infarction. J Am Coll Cardiol 63:110–122.
56. Martinsen BJ. 2005. Reference guide to the stages of chick heart embryology. Dev Dyn 233:1217–1237.
57. Matsuura K, Nagai T, Nishigaki N, Oyama T, Nishi J, Wada H, Sano M, Toko H, Akazawa H, Sato T, Nakaya H, Kasanuki H, Komuro I. 2004. Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279:11384–11391.
58. McDevitt TC, Laflamme MA, Murry CE. 2005. Proliferation of cardiomyocytes derived from human embryonic stem cells is mediated via the IGF/PI 3-kinase/Akt signaling pathway. J Mol Cell Cardiol 39:865–873.
59. Meilhac SM, Lescroart F, Blanpain C, Buckingham ME. 2015. Cardiac cell lineages that form the heart. Cold Spring Harb Perspect Med 5:a026344.
60. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, Hecker H, Schaefer A, Arseniev L, Hertenstein B, Ganser A, Drexler H. 2006. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation 113:1287–1294.
61. Mollova M, Bersell K, Walsh S, Savla J, Das LT, Park S-Y, Silberstein LE, Dos Remedios CG, Graham D, Colan S, Kühn B. 2013. Cardiomyocyte proliferation contributes to heart growth in young humans. Proc Natl Acad Sci U S A 110:1446–1451.
62. Moorman A, Webb S, Brown NA, Lamers W, Anderson RH. 2003. Development of the heart: (1) formation of the cardiac chambers and arterial trunks. Heart 89:806–814.
63. Mosimann C, Panáková D, Werdich AA, Musso G, Burger A, Lawson KL, Carr LA, Nevis KR, Sabeh MK, Zhou Y, Davidson AJ, DiBiase A, Burns CE, Burns CG, Macrae CA, Zon LI. 2015. Chamber identity programs drive early functional partitioning of the heart. Nat Commun 6:8146.
64. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després J-P, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB, American Heart Association Statistics Committee and Stroke Statistics Subcommittee. 2015. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation 131:e29–e322.
65. Muraoka N, Ieda M. 2015. Stoichiometry of transcription factors is critical for cardiac reprogramming. Circ Res 116:216–218.
66. Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KBS, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ. 2004. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428:664–668.
67. Nam Y-J, Song K, Luo X, Daniel E, Lambeth K, West K, Hill JA, DiMaio JM, Baker LA, Bassel-Duby R, Olson EN. 2013. Reprogramming of human fibroblasts toward a cardiac fate. Proc Natl Acad Sci U S A 110:5588–5593.
68. Noseda M, Peterkin T, Simões FC, Patient R, Schneider MD. 2011. Cardiopoietic factors: extracellular signals for cardiac lineage commitment. Circ Res 108:129–152.
69. Nygren JM, Jovinge S, Breitbach M, Säwén P, Röll W, Hescheler J, Taneera J, Fleischmann BK, Jacobsen SEW. 2004. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 10:494–501.
70. O'Meara CC, Wamstad JA, Gladstone RA, Fomovsky GM, Butty VL, Shrikumar A, Gannon JB, Boyer LA, Lee RT. 2015. Transcriptional reversion of cardiac myocyte fate during mammalian cardiac regeneration. Circ Res 116:804–815.
71. 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.
72. Perin EC, Sanz-Ruiz R, Sánchez PL, Lasso J, Pérez-Cano R, Alonso-Farto JC, Pérez-David E, Fernández-Santos ME, Serruys PW, Duckers HJ, Kastrup J, Chamuleau S, Zheng Y, Silva GV, Willerson JT, Fernández-Avilés F. 2014. Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: The PRECISE Trial. Am Heart J 168:88–95.e2.
73. Perin EC, Willerson JT, Pepine CJ, Henry TD, Ellis SG, Zhao DXM, Silva GV, Lai D, Thomas JD, Kronenberg MW, Martin AD, Anderson RD, Traverse JH, Penn MS, Anwaruddin S, Hatzopoulos AK, Gee AP, Taylor DA, Cogle CR, Smith D, Westbrook L, Chen J, Handberg E, Olson RE, Geither C, Bowman S, Francescon J, Baraniuk S, Piller LB, Simpson LM, Loghin C, Aguilar D, Richman S, Zierold C, Bettencourt J, Sayre SL, Vojvodic RW, Skarlatos SI, Gordon DJ, Ebert RF, Kwak M, Moyé LA, Simari RD, Cardiovascular Cell Therapy Research Network (CCTRN). 2012. Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial. JAMA 307:1717–1726.
74. Pfister O, Oikonomopoulos A, Sereti K-I, Sohn RL, Cullen D, Fine GC, Mouquet F, Westerman K, Liao R. 2008. Role of the ATP-binding cassette transporter Abcg2 in the phenotype and function of cardiac side population cells. Circ Res 103:825–835.
75. 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.
76. Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, Conway SJ, Fu J.D, Srivastava D. 2013. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 485:593–598.
77. Rana MS, Théveniau-Ruissy M, De Bono C, Mesbah K, Francou A, Rammah M, Domínguez JN, Roux M, Laforest B, Anderson RH, Mohun T, Zaffran S, Christoffels VM, Kelly RG. 2014. Tbx1 coordinates addition of posterior second heart field progenitor cells to the arterial and venous poles of the heart. Circ Res 115:790–799.
78. Rentschler S, Yen AH, Lu J, Petrenko NB, Lu MM, Manderfield LJ, Patel VV, Fishman GI, Epstein JA. 2012. Myocardial Notch signaling reprograms cardiomyocytes to a conduction-like phenotype. Circulation 126:1058–1066.
79. Robertson C, Tran DD, George SC. 2013. Concise review: maturation phases of human pluripotent stem cell-derived cardiomyocytes. Stem Cells 31:829–837.
80. Rota M, Padin-Iruegas ME, Misao Y, De Angelis A, Maestroni S, Ferreira-Martins J, Fiumana E, Rastaldo R, Arcarese ML, Mitchell TS, Boni A, Bolli R, Urbanek K, Hosoda T, Anversa P, Leri A, Kajstura J. 2008. Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function. Circ Res 103:107–116.
81. Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Hölschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Süselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM, REPAIR-AMI Investigators. 2006. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355:1210–1221.
82. Schlange T, Andrée B, Arnold HH, Brand T. 2000. BMP2 is required for early heart development during a distinct time period. Mech Dev 91:259–270.
83. Seyres D, Röder L, Perrin L. 2012. Genes and networks regulating cardiac development and function in flies: genetic and functional genomic approaches. Brief Funct Genomics 11:366–374.
84. Sinnecker D, Laugwitz K-L, Moretti A. 2014. Induced pluripotent stem cell-derived cardiomyocytes for drug development and toxicity testing. Pharmacol Ther 143:246–252.
85. Smith RR, Barile L, Cho HC, Leppo MK, Hare JM, Messina E, Giacomello A, Abraham MR, Marbán E. 2007. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation 115:896–908.
86. Smolich JJ. 1995. Ultrastructural and functional features of the developing mammalian heart: a brief overview. Reprod Fertil Dev 7:451–461.
87. Snir M, Kehat I, Gepstein A, Coleman R, Itskovitz-Eldor J, Livne E, Gepstein L. 2003. Assessment of the ultrastructural and proliferative properties of human embryonic stem cell-derived cardiomyocytes. Am J Physiol Heart Circ Physiol 285:H2355–H2363.
88. Song K, Nam Y-J, Luo X, Qi X, Tan W, Huang GN, Acharya A, Smith CL, Tallquist MD, Neilson EG, Hill JA, Bassel-Duby R, Olson EN. 2012. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature 485:599–604.
89. Später D, Abramczuk MK, Buac K, Zangi L, Stachel MW, Clarke J, Sahara M, Ludwig A, Chien KR. 2013. A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells. Nat Cell Biol 15:1098–1106.
90. Später D, Hansson EM, Zangi L, Chien KR. 2014. How to make a cardiomyocyte. Development 141:4418–4431.
91. Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, Kirk R, Rahmel AO, Hertz MI. 2011. The registry of the international society for heart and lung transplantation: twenty-eighth adult heart transplant report--2011. J Heart Lung Transplant 30:1078–1094.
92. Stewart S, MacIntyre K, Hole DJ, Capewell S, McMurray JJ. 2001. More “malignant” than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 3:315–322.
93. Sultana N, Zhang L, Yan J, Chen J, Cai W, Razzaque S, Jeong D, Sheng W, Bu L, Xu M, Huang G-Y, Hajjar RJ, Zhou B, Moon A, Cai CL. 2015. Resident c-kit(+) cells in the heart are not cardiac stem cells. Nat Commun 6:8701.
94. Sumi T, Tsuneyoshi N, Nakatsuji N, Suemori H. 2008. Defining early lineage specification of human embryonic stem cells by the orchestrated balance of canonical Wnt/beta-catenin, Activin/Nodal and BMP signaling. Development 135:2969–2979.
95. Sutton MG, Sharpe N. 2000. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 101:2981–2988.
96. Tada S, Era T, Furusawa C, Sakurai H, Nishikawa S, Kinoshita M, Nakao K, Chiba T, Nishikawa S-I. 2005. Characterization of mesendoderm: a diverging point of the definitive endoderm and mesoderm in embryonic stem cell differentiation culture. Development 132:4363–4374.
97. Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676.
98. Takeuchi JK, Bruneau BG. 2009. Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 459:708–711.
99. Tandon P, Miteva YV, Kuchenbrod LM, Cristea IM, Conlon FL. 2013. Tcf21 regulates the specification and maturation of proepicardial cells. Development 140:2409–2421.
100. Tang X-L, Rokosh G, Sanganalmath SK, Yuan F, Sato H, Mu J, Dai S, Li C, Chen N, Peng Y, Dawn B, Hunt G, Leri A, Kajstura J, Tiwari S, Shirk G, Anversa P, Bolli R. 2010. Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation 121:293–U235.
101. The Lancet Editors. 2014. Expression of concern: the SCIPIO trial. Lancet 383:1279.
102. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM, 1998. Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147.
103. Tian T, Chen B, Xiao Y, Yang K, Zhou X. 2014. Intramyocardial autologous bone marrow cell transplantation for ischemic heart disease: a systematic review and meta-analysis of randomized controlled trials. Atherosclerosis 233:485–492.
104. Tohyama S, Hattori F, Sano M, Hishiki T, Nagahata Y, Matsuura T, Hashimoto H, Suzuki T, Yamashita H, Satoh Y, Egashira T, Seki T, Muraoka N, Yamakawa H, Ohgino Y, Tanaka T, Yoichi M, Yuasa S, Murata M, Suematsu M, Fukuda K. 2013. Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell-derived cardiomyocytes. Cell Stem Cell 12:127–137.
105. Traverse JH, Henry TD, Ellis SG, Pepine CJ, Willerson JT, Zhao DXM, Forder JR, Byrne BJ, Hatzopoulos AK, Penn MS, Perin EC, Baran KW, Chambers J, Lambert C, Raveendran G, Simon DI, Vaughan DE, Simpson LM, Gee AP, Taylor DA, Cogle CR, Thomas JD, Silva GV, Jorgenson BC, Olson RE, Bowman S, Francescon J, Geither C, Handberg E, Smith DX, Baraniuk S, Piller LB, Loghin C, Aguilar D, Richman S, Zierold C, Bettencourt J, Sayre SL, Vojvodic RW, Skarlatos SI, Gordon DJ, Ebert RF, Kwak M, Moyé LA, Simari RD, Cardiovascular Cell Therapy Research Network. 2011. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial. JAMA 306:2110–2119.
106. Traverse JH, Henry TD, Pepine CJ, Willerson JT, Zhao DXM, Ellis SG, Forder JR, Anderson RD, Hatzopoulos AK, Penn MS, Perin EC, Chambers J, Baran KW, Raveendran G, Lambert C, Lerman A, Simon DI, Vaughan DE, Lai D, Gee AP, Taylor DA, Cogle CR, Thomas JD, Olson RE, Bowman S, Francescon J, Geither C, Handberg E, Kappenman C, Westbrook L, Piller LB, Simpson LM, Baraniuk S, Loghin C, Aguilar D, Richman S, Zierold C, Spoon DB, Bettencourt J, Sayre SL, Vojvodic RW, Skarlatos SI, Gordon DJ, Ebert RF, Kwak M, Moyé LA, Simari RD, Cardiovascular Cell Therapy Research Network (CCTRN). 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.
107. Urbanek K, Cesselli D, Rota M, Nascimbene A, De Angelis A, Hosoda T, Bearzi C, Boni A, Bolli R, Kajstura J, Anversa P, Leri A. 2006. Stem cell niches in the adult mouse heart. Proc Natl Acad Sci U S A 103:9226–9231.
108. van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J, Lin S-CJ, Middleton RC, Marbán E, Molkentin JD. 2014. c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature 509:337–341.
109. van Vliet P, Wu SM, Zaffran S, Pucéat M. 2012. Early cardiac development: a view from stem cells to embryos. Cardiovasc Res 96:352–362.
110. Vincent SD, Buckingham ME. 2010. How to make a heart: the origin and regulation of cardiac progenitor cells. Curr Top Dev Biol 90:1–41.
111. Von Gise A, Zhou B, Honor LB, Ma Q, Petryk A, Pu WT. 2011. WT1 regulates epicardial epithelial to mesenchymal transition through β-catenin and retinoic acid signaling pathways. Dev Biol 356:421–431.
112. Wang J, Cao J, Dickson AL, Poss KD. 2015. Epicardial regeneration is guided by cardiac outflow tract and Hedgehog signalling. Nature 522:226–230.
113. 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.
114. White IA, Gordon J, Balkan W, Hare JM. 2015. Sympathetic Reinnervation Is Required for Mammalian Cardiac Regeneration. Circ Res 117:990–994.
115. Willems E, Leyns L. 2008. Patterning of mouse embryonic stem cell-derived pan-mesoderm by Activin A/Nodal and Bmp4 signaling requires Fibroblast Growth Factor activity. Differentiation 76:745–759.
116. Xin M, Olson EN, Bassel-Duby R. 2013. Mending broken hearts:cardiac development as a basis foradult heart regeneration and repair. Nature Publishing Group 14:529–541.
117. Yang L, Soonpaa MH, Adler ED, Roepke TK, Kattman SJ, Kennedy M, Henckaerts E, Bonham K, Abbott GW, Linden RM, Field LJ, Keller GM. 2008. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature 453:524–528.
118. Zak R. 1973. Cell proliferation during cardiac growth. Am J Cardiol 31:211–219.
119. Zhang Liying, Guo J, Zhang P, Xiong Q, Wu SC, Xia L, Roy SS, Tolar J, O'Connell TD, Kyba M, Liao K, Zhang J. 2015. Derivation and high engraftment of patient-specific cardiomyocyte sheet using induced pluripotent stem cells generated from adult cardiac fibroblast. Circ Heart Fail 8:156–166.
120. Zhang L, Nomura-Kitabayashi A, Sultana N, Cai W, Cai X, Moon AM, Cai C-L. 2014. Mesodermal Nkx2.5 is necessary and sufficient for early second heart field development. Dev Biol 390:68–79.