Heart Failure Reviews

, Volume 24, Issue 1, pp 133–142 | Cite as

Cell-based therapies for the treatment of myocardial infarction: lessons from cardiac regeneration and repair mechanisms in non-human vertebrates

  • Paul Palmquist-Gomes
  • José María Pérez-Pomares
  • Juan Antonio GuadixEmail author


Ischemic cardiomyopathy is the cardiovascular condition with the highest impact on the Western population. In mammals (humans included), prolonged ischemia in the ventricular walls causes the death of cardiomyocytes (myocardial infarction, MI). The loss of myocardial mass is soon compensated by the formation of a reparative, non-contractile fibrotic scar that ultimately affects heart performance. Despite the enormous clinical relevance of MI, no effective therapy is available for the long-term treatment of this condition. Moreover, since the human heart is not able to undergo spontaneous regeneration, many researchers aim at designing cell-based therapies that allow for the substitution of dead cardiomyocytes by new, functional ones. So far, the majority of such strategies rely on the injection of different progenitor/stem cells to the infarcted heart. These cardiovascular progenitors, which are expected to differentiate into cardiomyocytes de novo, seldom give rise to new cardiac muscle. In this context, the most important challenge in the field is to fully disclose the molecular and cellular mechanisms that could promote active myocardial regeneration after cardiac damage. Accordingly, we suggest that such strategy should be inspired by the unique regenerative and reparative responses displayed by non-human animal models, from the restricted postnatal myocardial regeneration abilities of the murine heart to the full ventricular regeneration of some bony fishes (e.g., zebrafish). In this review article, we will discuss about current scientific approaches to study cardiac reparative and regenerative phenomena using animal models.


Myocardial infarction Cell-based therapies Tissue regeneration Tissue repair Animal models 



We thank all present and past members of our laboratory for fruitful discussions.


This work was supported by the Spanish Ministry of Economy (MINECO) [grant number BFU2015-65783-R] and [grant number SAF2015-71863] (to JMPP); Instituto de Salud Carlos III (MINECO-ISCIII) [grant number RD16/0011/0030-TERCEL] (to JMPP); Plan Propio-Universidad de Málaga (to JAG); Spanish Society of Cardiology grant, “Proyectos de la SEC para Investigación Básica en Cardiología 2018” (to JAG).

Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interest.


  1. 1.
    Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, Ferranti S, De Després JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jiménez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, MacKey RH, Magid DJ, McGuire DK, Mohler ER, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB (2016) Heart disease and stroke statistics-2016 update a report from the American Heart Association. Circulation 133:e38–e48. CrossRefPubMedGoogle Scholar
  2. 2.
    Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P, Baumbach A, Bugiardini R, Coman IM, Delgado V, Fitzsimons D, Gaemperli O, Gershlick AH, Gielen S, Harjola VP, Katus HA, Knuuti J, Kolh P, Leclercq C, Lip GYH, Morais J, Neskovic AN, Neumann FJ, Niessner A, Piepoli MF, Richter DJ, Shlyakhto E, Simpson IA, Steg PG, Terkelsen CJ, Thygesen K, Windecker S, Zamorano JL, Zeymer U (2018) 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 39:119–177. CrossRefPubMedGoogle Scholar
  3. 3.
    Jessup M, Brozena S (2003) Heart failure. N Engl J Med 348:2007–2018CrossRefGoogle Scholar
  4. 4.
    Hall R, Simpson I (2009) The ESC textbook of cardiovascular medicine: second edition. Oxford Univ Press, Oxford. CrossRefGoogle Scholar
  5. 5.
    Taylor DO, Edwards LB, Boucek MM, Trulock EP, Aurora P, Christie J, Dobbels F, Rahmel AO, Keck BM, Hertz MI (2007) Registry of the International Society for Heart and Lung Transplantation: Twenty-fourth Official Adult Heart Transplant report-2007. J Hear Lung Transplant 26:769–781. CrossRefGoogle Scholar
  6. 6.
    Sager HB, Kessler T, Schunkert H (2017) Monocytes and macrophages in cardiac injury and repair. J Thorac Dis 9:S30–S35. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ruiz-Villalba A, Simón AM, Pogontke C, Castillo MI, Abizanda G, Pelacho B, Sánchez-Domínguez R, Segovia JC, Prósper F, Pérez-Pomares JM (2015) Interacting resident epicardium-derived fibroblasts and recruited bone marrow cells form myocardial infarction scar. J Am Coll Cardiol 65:2057–2066. CrossRefPubMedGoogle Scholar
  8. 8.
    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. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    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. CrossRefPubMedGoogle Scholar
  10. 10.
    Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, Battaglia M, Latronico MVG, Coletta M, Vivarelli E, Frati L, Cossu G, Giacomello A (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95:911–921. CrossRefPubMedGoogle Scholar
  11. 11.
    Lai AG, Aboobaker AA (2017) EvoRegen in animals: time to uncover deep conservation or convergence of adult stem cell evolution and regenerative processes. Dev Biol 433:118–131. CrossRefPubMedGoogle Scholar
  12. 12.
    Sehring IM, Jahn C, Weidinger G (2016) Zebrafish fin and heart: what’s special about regeneration? Curr Opin Genet Dev 40:48–56. CrossRefPubMedGoogle Scholar
  13. 13.
    Godwin JW, Rosenthal N (2014) Scar-free wound healing and regeneration in amphibians: immunological influences on regenerative success. Differentiation 87:66–75. CrossRefPubMedGoogle Scholar
  14. 14.
    Galliot B, Crescenzi M, Jacinto A, Tajbakhsh S (2017) Trends in tissue repair and regeneration. Development 144:357–364. CrossRefPubMedGoogle Scholar
  15. 15.
    Grivas J, Haag M, Johnson A, Manalo T, Roell J, Das TL, Brown E, Burns AR, Lafontant PJ (2014) Cardiac repair and regenerative potential in the goldfish (Carassius auratus) heart. Comp Biochem Physiol Part C Toxicol Pharmacol 163:14–23. CrossRefGoogle Scholar
  16. 16.
    Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298:2188–2190. CrossRefPubMedGoogle Scholar
  17. 17.
    Jopling C, Sleep E, Raya M, Martí M, Raya A, Belmonte JCI (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464:606–609. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Vargas-González A, Prado-Zayago E, León-Olea M, Guarner-Lans V, Cano-Martínez A (2005) Regeneración miocárdica en Ambystoma mexicanum después de lesión quirúrgica. Arch Cardiol Mex 75:21–29Google Scholar
  19. 19.
    Witman N, Murtuza B, Davis B, Arner A, Morrison JI (2011) Recapitulation of developmental cardiogenesis governs the morphological and functional regeneration of adult newt hearts following injury. Dev Biol 354:67–76. CrossRefPubMedGoogle Scholar
  20. 20.
    Sánchez-Iranzo H, Galardi-Castilla M, Minguillón C, Sanz-Morejón A, González-Rosa JM, Felker A, Ernst A, Guzmán-Martínez G, Mosimann C, Mercader N (2018) Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration. Nat Commun 9:428. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sallin P, de Preux Charles AS, Duruz V, Pfefferli C, Jaźwińska A (2015) A dual epimorphic and compensatory mode of heart regeneration in zebrafish. Dev Biol 399:27–40. CrossRefPubMedGoogle Scholar
  22. 22.
    Patterson M, Barske L, Van Handel B, Rau CD, Gan P, Sharma A, Parikh S, Denholtz M, Huang Y, Yamaguchi Y, Shen H, Allayee H, Crump JG, Force TI, Lien CL, Makita T, Lusis AJ, Kumar SR, Sucov HM (2017) Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration. Nat Genet 49:1346–1353. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Ito K, Morioka M, Kimura S, Tasaki M, Inohaya K, Kudo A (2014) Differential reparative phenotypes between zebrafish and medaka after cardiac injury. Dev Dyn 243:1106–1115. CrossRefPubMedGoogle Scholar
  24. 24.
    Reyer R (1954) Regeneration of the lens in amphibians. Q Rev Biol 29:1–46CrossRefGoogle Scholar
  25. 25.
    Young HE, Bailey CF, Markwald RR, Dalley BK (1985) Histological analysis of limb regeneration in postmetamorphic adult Ambystoma. Anat Rec 212:183–194CrossRefGoogle Scholar
  26. 26.
    Ghosh S, Thorogood P, Ferretti P (1994) Regenerative capability of upper and lower jaws in the newt. Int J Dev Biol 38:479–490PubMedGoogle Scholar
  27. 27.
    Mitashov VI (1996) Mechanisms of retina regeneration in urodeles. Int J Dev Biol 40:833–844PubMedGoogle Scholar
  28. 28.
    Liao S, Dong W, Lv L, Guo H, Yang J, Zhao H, Huang R, Yuan Z, Chen Y, Feng S, Zheng X, Huang J, Huang W, Qi X, Cai D (2017) Heart regeneration in adult Xenopus tropicalis after apical resection. Cell Biosci 7:1–16. CrossRefGoogle Scholar
  29. 29.
    Marshall L, Vivien C, Girardot F, Péricard L, Demeneix BA, Coen L, Chai N (2017) Persistent fibrosis, hypertrophy and sarcomere disorganisation after endoscopyguided heart resection in adult Xenopus. PLoS One 12:1–24. CrossRefGoogle Scholar
  30. 30.
    Marshall L, Girardot F, Demeneix BA, Coen L (2018) Is adult cardiac regeneration absent in Xenopus laevis yet present in Xenopus tropicalis? Cell Biosci 8:1–4. CrossRefGoogle Scholar
  31. 31.
    Liao S, Dong W, Zhao H, Huang R, Qi X, Cai D (2018) Cardiac regeneration in Xenopus tropicalis and Xenopus laevis: discrepancies and problems. Cell Biosci 8:32. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Sallin P, Jaźwińska A (2016) Acute stress is detrimental to heart regeneration in zebrafish. Open Biol 6:160012. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Flink IL (2002) Cell cycle reentry of ventricular and atrial cardiomyocytes and cells within the epicardium following amputation of the ventricular apex in the axolotl, Amblystoma mexicanum: confocal microscopic immunofluorescent image analysis of bromodeoxyuridine-label. Anat Embryol (Berl) 205:235–244. CrossRefGoogle Scholar
  34. 34.
    Cano-Martínez A, Vargas-González A, Guarner-Lans V, Prado-Zayago E, León-Olea M, Nieto-Lima B (2010) Functional and structural regeneration in the axolotl heart (Ambystoma mexicanum) after partial ventricular amputation. Arch Cardiol Mex 80:79–86PubMedGoogle Scholar
  35. 35.
    Oberpriller J, Oberpriller J (1974) Response of the adult newt ventricle to injury. J Exp Zool 187:249–253. CrossRefPubMedGoogle Scholar
  36. 36.
    Neff AW, Dent AE, Armstrong JB (1996) Heart development in urodeles. Science 725:719–725Google Scholar
  37. 37.
    Porrello ER, Olson EN (2014) A neonatal blueprint for cardiac regeneration. Stem Cell Res 13:556–570. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Bryant DM, O’Meara CC, Ho NN, Gannon J, Cai L, Lee RT (2015) A systematic analysis of neonatal mouse heart regeneration after apical resection. J Mol Cell Cardiol 79:315–318. CrossRefPubMedGoogle Scholar
  39. 39.
    Darehzereshki A, Rubin N, Gamba L, Kim J, Fraser J, Huang Y, Billings J, Mohammadzadeh R, Wood J, Warburton D, Kaartinen V, Lien C-L (2015) Differential regenerative capacity of neonatal mouse hearts after cryoinjury. Dev Biol 399:91–99. CrossRefPubMedGoogle Scholar
  40. 40.
    Sousounis K, Baddour JA, Tsonis PA (2014) Aging and regeneration in vertebrates, 1st ed. Elsevier Inc, AmsterdamGoogle Scholar
  41. 41.
    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. CrossRefPubMedGoogle Scholar
  42. 42.
    Eschenhagen T, Bolli R, Braun T, Field LJ, Fleischmann BK, Frisén J, Giacca M, Hare JM, Houser S, Lee RT, Marbán E, Martin JF, Molkentin JD, Murry CE, Riley PR, Ruiz-Lozano P, Sadek HA, Sussman MA, Hill JA (2017) Cardiomyocyte regeneration. Circulation 136:680–686. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    McBrearty B a, Clark LD, Zhang XM, Blankenhorn EP, Heber-Katz E (1998) Genetic analysis of a mammalian wound-healing trait. Proc Natl Acad Sci U S A 95:11792–11797. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Leferovich JM, Bedelbaeva K, Samulewicz S, Zhang XM, Zwas D, Lankford EB, Heber-Katz E (2001) Heart regeneration in adult MRL mice. Proc Natl Acad Sci U S A 98:9830–9835. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Morgan TH (1901) Regeneration. Columbia Univ Biol Ser VII:1–316Google Scholar
  46. 46.
    Haque ZK, Wang DZ (2017) How cardiomyocytes sense pathophysiological stresses for cardiac remodeling. Cell Mol Life Sci 74:983–1000. CrossRefPubMedGoogle Scholar
  47. 47.
    Bettencourt-Dias M, Mittnacht S, Brockes JP (2003) Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes. J Cell Sci 116:4001–4009. CrossRefPubMedGoogle Scholar
  48. 48.
    Lepilina A, Coon AN, Kikuchi K, Holdway JE, Roberts RW, Burns CG, Poss KD (2006) A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Cell 127:607–619. CrossRefPubMedGoogle Scholar
  49. 49.
    Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Walsh S, Zupicich J, Alkass K, Buchholz BA, Jovinge S, Frisén J, Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabi-heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisnt J (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Pasumarthi KBS, Field LJ (2002) Cardiomyocyte cell cycle regulation. Circ Res 90:1044–1054. CrossRefPubMedGoogle Scholar
  51. 51.
    Ramkisoensing AA, De Vries AAF, Atsma DE, Schalij MJ, Pijnappels DA (2014) Interaction between myofibroblasts and stem cells in the fibrotic heart: balancing between deterioration and regeneration. Cardiovasc Res 102:224–231. CrossRefPubMedGoogle Scholar
  52. 52.
    Slack JM (2000) Stem cells in epithelial tissues. Science 287:1431–1433. CrossRefPubMedGoogle Scholar
  53. 53.
    Martin CM, Meeson AP, Robertson SM, Hawke TJ, Richardson JA, Bates S, Goetsch SC, Gallardo TD, Garry DJ (2004) Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev Biol 265:262–275. CrossRefPubMedGoogle Scholar
  54. 54.
    Laugwitz K-L, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin L-Z, Cai C-L, Lu MM, Reth M, Platoshyn O, Yuan JX-J, Evans S, Chien KR (2005) Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433:647–653. CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    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. CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Czarna A, Sanada F, Matsuda A, Kim J, Signore S, Pereira JD, Sorrentino A, Kannappan R, Cannatà A, Hosoda T, Rota M, Crea F, Anversa P, Leri A (2017) Single-cell analysis of the fate of c-kit-positive bone marrow cells. npj Regen Med 2:27. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Laugwitz K-L, Moretti A, Caron L, Nakano A, Chien KR (2007) Islet1 cardiovascular progenitors: a single source for heart lineages? Development 135:193–205. CrossRefGoogle Scholar
  58. 58.
    Wessels A, Pérez-Pomares JM (2004) The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. Anat Rec Part A Discov Mol Cell Evol Biol 276A:43–57. CrossRefGoogle Scholar
  59. 59.
    Bilbija D, Haugen F, Sagave J, Baysa A, Bastani N, Levy FO, Sirsjö A, Blomhoff R, Valen G (2012) Retinoic acid signalling is activated in the postischemic heart and may influence Remodelling. PLoS One 7:1–9. CrossRefGoogle Scholar
  60. 60.
    Wei K, Serpooshan V, Hurtado C, Diez-Cunado M, Zhao M, Maruyama S, Zhu W, Fajardo G, Noseda M, Nakamura K, Tian X, Liu Q, Wang A, Matsuura Y, Bushway P, Cai W, Savchenko A, Mahmoudi M, Schneider MD, Van Den Hoff MJB, Butte MJ, Yang PC, Walsh K, Zhou B, Bernstein D, Mercola M, Ruiz-Lozano P (2015) Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature 525:479–485. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Cao J, Poss KD (2018) The epicardium as a hub for heart regeneration. Nat Rev Cardiol 8:53–69. CrossRefGoogle Scholar
  62. 62.
    Leri A, Rota M, Hosoda T, Goichberg P, Anversa P (2014) Cardiac stem cell niches. Stem Cell Res 13:631–646. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Drenckhahn JD, Schwarz QP, Gray S, Laskowski A, Kiriazis H, Ming Z, Harvey RP, Du XJ, Thorburn DR, Cox TC (2008) Compensatory growth of healthy cardiac cells in the presence of diseased cells restores tissue homeostasis during heart development. Dev Cell 15:521–533. CrossRefPubMedGoogle Scholar
  64. 64.
    Sturzu AC, Rajarajan K, Passer D, Plonowska K, Riley A, Tan TC, Sharma A, Xu AF, Engels MC, Feistritzer R, Li G, Selig MK, Geissler R, Robertson KD, Scherrer-Crosbie M, Domian IJ, Wu SM (2015) Fetal mammalian heart generates a robust compensatory response to cell loss. Circulation 132:109–121. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Palmquist-Gomes P, Guadix JA, Pérez-Pomares JM (2016) A chick embryo cryoinjury model for the study of embryonic organ development and repair. Differentiation 91:72–77. CrossRefPubMedGoogle Scholar
  66. 66.
    Guadix JA, Zugaza JL, Gálvez-Martín P (2017) Characteristics, applications and prospects of mesenchymal stem cells in cell therapy. Med Clin 148:408–414. CrossRefGoogle Scholar
  67. 67.
    Brandão KO, Tabel VA, Atsma DE, Mummery CL, Davis RP (2017) Human pluripotent stem cell models of cardiac disease: from mechanisms to therapies. Dis Model Mech 10:1039–1059. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Oh H, Ito H, Sano S (2016) Challenges to success in heart failure: cardiac cell therapies in patients with heart diseases. J Cardiol 68:361–367. CrossRefPubMedGoogle Scholar
  69. 69.
    Loffredo FS, Steinhauser ML, Gannon J, Lee RT (2011) Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell 8:389–398. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Caplan A (2009) Why are MSCs therapeutic? New data: new insight. J Pathol 217:318–324. CrossRefPubMedGoogle Scholar
  71. 71.
    Abdel-latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B (2007) Adult bone marrow–derived cells for cardiac repair. Arch Intern Med 167:989–997. CrossRefPubMedGoogle Scholar
  72. 72.
    Posfai E, Tam OH, Rossant J (2014) Mechanisms of pluripotency in vivo and in vitro. In: Current Topics in Developmental Biology, 1st ed. Elsevier Inc., Amsterdam, pp 1–37Google Scholar
  73. 73.
    Fong C-Y, Gauthaman K, Bongso A (2010) Teratomas from pluripotent stem cells: a clinical hurdle. J Cell Biochem 111:769–781. CrossRefPubMedGoogle Scholar
  74. 74.
    Romano G, Morales F, Marino IR, Giordano A (2014) A commentary on iPS cells: potential applications in autologous transplantation, study of illnesses and drug screening. J Cell Physiol 229:148–152. CrossRefPubMedGoogle Scholar
  75. 75.
    Klose K, Gossen M, Stamm C (2018) Turning fibroblasts into cardiomyocytes: technological review of cardiac transdifferentiation strategies. FASEB J:fj.201800712R.
  76. 76.
    Tani H, Sadahiro T, Ieda M (2018) Direct cardiac reprogramming: a novel approach for heart regeneration. Int J Mol Sci 19(9).
  77. 77.
    Nam YJ, 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 110:5588–5593. CrossRefPubMedGoogle Scholar
  78. 78.
    Jesty S a, Steffey M a, 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 109:13380–13385. CrossRefPubMedGoogle Scholar
  79. 79.
    Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, Czer LS, 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. CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    van Rooij E, Olson EN (2012) MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat Rev Drug Discov 11:860–872. CrossRefPubMedGoogle Scholar
  81. 81.
    Porrello ER, Mahmoud AI, Simpson E, Johnson BA, Grinsfelder D, Canseco D, Mammen PP, Rothermel BA, Olson EN, Sadek HA (2013) Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. Proc Natl Acad Sci 110:187–192. CrossRefPubMedGoogle Scholar
  82. 82.
    Mohamed TMA, Ang YS, Radzinsky E, Zhou P, Huang Y, Elfenbein A, Foley A, Magnitsky S, Srivastava D (2018) Regulation of cell cycle to stimulate adult cardiomyocyte proliferation and cardiac regeneration. Cell 173(1):104–116. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Paul Palmquist-Gomes
    • 1
    • 2
  • José María Pérez-Pomares
    • 1
    • 2
  • Juan Antonio Guadix
    • 1
    • 2
    Email author
  1. 1.Department of Animal Biology, Faculty of SciencesUniversity of Málaga, Instituto Malagueño de Biomedicina (IBIMA)MálagaSpain
  2. 2.BIONAND, Centro Andaluz de Nanomedicina y Biotecnología (Junta de Andalucía, Universidad de Málaga)MálagaSpain

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