Skip to main content
SpringerLink
Log in

microRNA and Cardiac Regeneration

  • Chapter
microRNA: Basic Science

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 887))

Abstract

Heart diseases are a very common health problem in developed as well as developing countries. In particular, ischemic heart disease and heart failure represent a plague for the patients and for the society. Loss of cardiac tissue after myocardial infarction or dysfunctioning tissue in nonischemic cardiomyopathies may result in cardiac failure. Despite great advancements in the treatment of these diseases, there is a substantial unmet need for novel therapies, ideally addressing repair and regeneration of the damaged or lost myocardium. Along this line, cardiac cell based therapies have gained substantial attention. Three main approaches are currently under investigation: stem cell therapy with either embryonic or adult stem cells; generation of patient-specific induced pluripotent stem cells; stimulation of endogenous regeneration trough direct reprogramming of fibroblasts into cardiomyocytes, activation of resident cardiac stem cells or induction of native resident cardiomyocytes to reenter the cell cycle. All these strategies need to be optimized since their efficiency is low.

It has recently become clear that cardiac signaling and transcriptional pathways are intimately intertwined with microRNA molecules which act as modulators of cardiac development, function, and disease. Moreover, miRNA also regulates stem cell differentiation. Here we describe how miRNA may circumvent hurdles that hamper the field of cardiac regeneration and stem cell therapy, and how miRNA may result as the most suitable solution for the damaged heart.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Braunwald E, Antman EM. Evidence-based coronary care. Ann Intern Med. 1997;126:551–3.

    Article  CAS  PubMed  Google Scholar 

  2. Braunwald E. Shattuck lecture—cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med. 1997;337:1360–9.

    Article  CAS  PubMed  Google Scholar 

  3. Costanzo MR. The role of histoincompatibility in cardiac allograft vasculopathy. J Heart Lung Transplant. 1995;14:S180–4.

    CAS  PubMed  Google Scholar 

  4. Costanzo MR, Augustine S, Bourge R, et al. Selection and treatment of candidates for heart transplantation. A statement for health professionals from the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association. Circulation. 1995;92:3593–612.

    Article  CAS  PubMed  Google Scholar 

  5. Ounzain S, Crippa S, Pedrazzini T. Small and long non-coding RNAs in cardiac homeostasis and regeneration. Biochim Biophys Acta. 1833;2013:923–33.

    Google Scholar 

  6. Oberpriller JO, Oberpriller JC. Response of the adult newt ventricle to injury. J Exp Zool. 1974;187:249–53.

    Article  CAS  PubMed  Google Scholar 

  7. Poss KD, Wilson LG, Keating MT. Heart regeneration in zebrafish. Science. 2002;298:2188–90.

    Article  CAS  PubMed  Google Scholar 

  8. Chablais F, Jazwinska A. The regenerative capacity of the zebrafish heart is dependent on TGFbeta signaling. Development. 2012;139:1921–30.

    Article  CAS  PubMed  Google Scholar 

  9. Gonzalez-Rosa JM, Martin V, Peralta M, Torres M, Mercader N. Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish. Development. 2011;138:1663–74.

    Article  CAS  PubMed  Google Scholar 

  10. Wang J, Panakova D, Kikuchi K, et al. The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Development. 2011;138:3421–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jopling C, Sleep E, Raya M, Marti M, Raya A, Izpisua Belmonte JC. Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature. 2010;464:606–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kikuchi K, Holdway JE, Werdich AA, et al. Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes. Nature. 2010;464:601–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Porrello ER, Mahmoud AI, Simpson E, et al. Transient regenerative potential of the neonatal mouse heart. Science. 2011;331:1078–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Holm S. The blastocyst transfer method cannot rescue human embryonic stem cell research. Am J Bioeth. 2005;5:20–1; discussion W10-3.

    Article  PubMed  Google Scholar 

  15. Kehat I, Kenyagin-Karsenti D, Snir M, et al. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest. 2001;108:407–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Arbel G, Caspi O, Huber I, Gepstein A, Weiler-Sagie M, Gepstein L. Methods for human embryonic stem cells derived cardiomyocytes cultivation, genetic manipulation, and transplantation. Methods Mol Biol. 2010;660:85–95.

    Article  CAS  PubMed  Google Scholar 

  17. Melo LG, Pachori AS, Kong D, et al. Molecular and cell-based therapies for protection, rescue, and repair of ischemic myocardium: reasons for cautious optimism. Circulation. 2004;109:2386–93.

    Article  PubMed  Google Scholar 

  18. Laflamme MA, Murry CE. Regenerating the heart. Nat Biotechnol. 2005;23:845–56.

    Article  CAS  PubMed  Google Scholar 

  19. Quevedo HC, Hatzistergos KE, Oskouei BN, et al. Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc Natl Acad Sci U S A. 2009;106:14022–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res. 2008;103:1204–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gnecchi M, He H, Liang OD, et al. Paracrine action accounts for marked protection of ischemic heart by akt-modified mesenchymal stem cells. Nat Med. 2005;11:367–8.

    Article  CAS  PubMed  Google Scholar 

  22. Gnecchi M, Danieli P, Cervio E. Mesenchymal stem cell therapy for heart disease. Vascul Pharmacol. 2012;57:48–55.

    Article  CAS  PubMed  Google Scholar 

  23. Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–76.

    Article  CAS  PubMed  Google Scholar 

  24. Nadal-Ginard B, Kajstura J, Leri A, Anversa P. Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res. 2003;92:139–50.

    Article  CAS  PubMed  Google Scholar 

  25. Ellison GM, Torella D, Dellegrottaglie S, et al. Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart. J Am Coll Cardiol. 2011;58:977–86.

    Article  CAS  PubMed  Google Scholar 

  26. Torella D, Ellison GM, Karakikes I, Nadal-Ginard B. Resident cardiac stem cells. Cell Mol Life Sci. 2007;64:661–73.

    Article  CAS  PubMed  Google Scholar 

  27. Hsieh PC, Segers VF, Davis ME, et al. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med. 2007;13:970–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ellison GM, Galuppo V, Vicinanza C, et al. Cardiac stem and progenitor cell identification: different markers for the same cell? Front Biosci (Schol Ed). 2010;2:641–52.

    Google Scholar 

  29. Messina E, De Angelis L, Frati G, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res. 2004;95:911–21.

    Article  CAS  PubMed  Google Scholar 

  30. Kong D, Melo LG, Mangi AA, et al. Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation. 2004;109:1769–75.

    Article  CAS  PubMed  Google Scholar 

  31. Herzog EL, Chai L, Krause DS. Plasticity of marrow-derived stem cells. Blood. 2003;102:3483–93.

    Article  CAS  PubMed  Google Scholar 

  32. Tosh D, Slack JM. How cells change their phenotype. Nat Rev Mol Cell Biol. 2002;3:187–94.

    Article  CAS  PubMed  Google Scholar 

  33. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  CAS  PubMed  Google Scholar 

  34. Gurdon JB, Melton DA. Nuclear reprogramming in cells. Science. 2008;322:1811–5.

    Article  CAS  PubMed  Google Scholar 

  35. Mauritz C, Schwanke K, Reppel M, et al. Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation. 2008;118:507–17.

    Article  PubMed  Google Scholar 

  36. Nelson TJ, Martinez-Fernandez A, Terzic A. Induced pluripotent stem cells: developmental biology to regenerative medicine. Nat Rev Cardiol. 2010;7:700–10.

    PubMed  Google Scholar 

  37. Zhang J, Wilson GF, Soerens AG, et al. Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res. 2009;104:e30–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Swijnenburg RJ, Govaert JA, van der Bogt KE, et al. Timing of bone marrow cell delivery has minimal effects on cell viability and cardiac recovery after myocardial infarction. Circ Cardiovasc Imaging. 2010;3:77–85.

    Article  PubMed  Google Scholar 

  39. Nelson TJ, Martinez-Fernandez A, Yamada S, Ikeda Y, Perez-Terzic C, Terzic A. Induced pluripotent stem cells: advances to applications. Stem Cells Cloning. 2010;3:29–37.

    CAS  PubMed  Google Scholar 

  40. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010;463:1035–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ieda M, Fu JD, Delgado-Olguin P, et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 2010;142:375–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fu JD, Stone NR, Liu L, et al. Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state. Stem Cell Reports. 2013;1:235–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Cai B, Li J, Wang J, et al. microRNA-124 regulates cardiomyocyte differentiation of bone marrow-derived mesenchymal stem cells via targeting STAT3 signaling. Stem Cells. 2012;30:1746–55.

    Article  CAS  PubMed  Google Scholar 

  44. Lee Y, Kim M, Han J, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23:4051–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Han J, Lee Y, Yeom KH, et al. Molecular basis for the recognition of primary microRNAs by the drosha-DGCR8 complex. Cell. 2006;125:887–901.

    Article  CAS  PubMed  Google Scholar 

  46. Ruby JG, Jan CH, Bartel DP. Intronic microRNA precursors that bypass Drosha processing. Nature. 2007;448:83–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gangaraju VK, Lin H. MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol. 2009;10:116–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Brennecke J, Stark A, Russell RB, Cohen SM. Principles of microRNA-target recognition. PLoS Biol. 2005;3, e85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Bartel B. MicroRNAs directing siRNA biogenesis. Nat Struct Mol Biol. 2005;12:569–71.

    Article  CAS  PubMed  Google Scholar 

  50. Hwang HW, Wentzel EA, Mendell JT. A hexanucleotide element directs microRNA nuclear import. Science. 2007;315:97–100.

    Article  CAS  PubMed  Google Scholar 

  51. Kim DH, Saetrom P, Snove Jr O, Rossi JJ. MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci U S A. 2008;105:16230–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007;318:1931–4.

    Article  CAS  PubMed  Google Scholar 

  53. Kozak M. Faulty old ideas about translational regulation paved the way for current confusion about how microRNAs function. Gene. 2008;423:108–15.

    Article  CAS  PubMed  Google Scholar 

  54. Eulalio A, Huntzinger E, Izaurralde E. Getting to the root of miRNA-mediated gene silencing. Cell. 2008;132:9–14.

    Article  CAS  PubMed  Google Scholar 

  55. Olson EN, Schneider MD. Sizing up the heart: development redux in disease. Genes Dev. 2003;17:1937–56.

    Article  CAS  PubMed  Google Scholar 

  56. Liu N, Olson EN. MicroRNA regulatory networks in cardiovascular development. Dev Cell. 2010;18:510–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Murchison EP, Partridge JF, Tam OH, Cheloufi S, Hannon GJ. Characterization of dicer-deficient murine embryonic stem cells. Proc Natl Acad Sci U S A. 2005;102:12135–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature. 2005;436:214–20.

    Article  CAS  PubMed  Google Scholar 

  59. Saxena A, Tabin CJ. miRNA-processing enzyme dicer is necessary for cardiac outflow tract alignment and chamber septation. Proc Natl Acad Sci U S A. 2010;107:87–91.

    Article  CAS  PubMed  Google Scholar 

  60. Knecht AK, Bronner-Fraser M. Induction of the neural crest: a multigene process. Nat Rev Genet. 2002;3:453–61.

    Article  CAS  PubMed  Google Scholar 

  61. Rao PK, Toyama Y, Chiang HR, et al. Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure. Circ Res. 2009;105:585–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kwon C, Han Z, Olson EN, Srivastava D. MicroRNA1 influences cardiac differentiation in drosophila and regulates notch signaling. Proc Natl Acad Sci U S A. 2005;102:18986–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhao Y, Ransom JF, Li A, et al. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1–2. Cell. 2007;129:303–17.

    Article  CAS  PubMed  Google Scholar 

  64. Chen J, Wang DZ. microRNAs in cardiovascular development. J Mol Cell Cardiol. 2012;52:949–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Porrello ER. microRNAs in cardiac development and regeneration. Clin Sci (Lond). 2013;125:151–66.

    Article  CAS  Google Scholar 

  66. van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science. 2007;316:575–9.

    Article  PubMed  CAS  Google Scholar 

  67. Callis TE, Pandya K, Seok HY, et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest. 2009;119:2772–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Montgomery RL, Hullinger TG, Semus HM, et al. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation. 2011;124:1537–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. van Rooij E, Quiat D, Johnson BA, et al. A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell. 2009;17:662–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Ventura A, Young AG, Winslow MM, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008;132:875–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Yelon D. Cardiac patterning and morphogenesis in zebrafish. Dev Dyn. 2001;222:552–63.

    Article  CAS  PubMed  Google Scholar 

  72. Srivastava D. Making or breaking the heart: from lineage determination to morphogenesis. Cell. 2006;126:1037–48.

    Article  CAS  PubMed  Google Scholar 

  73. Morton SU, Scherz PJ, Cordes KR, Ivey KN, Stainier DY, Srivastava D. microRNA-138 modulates cardiac patterning during embryonic development. Proc Natl Acad Sci U S A. 2008;105:17830–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Fish JE, Wythe JD, Xiao T, et al. A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish. Development. 2011;138:1409–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature. 2011;469:336–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Niwa H. Self-renewal and differentiation of ES cells. Hum Cell. 2000;13:161–75.

    CAS  PubMed  Google Scholar 

  77. Kopp JL, Ormsbee BD, Desler M, Rizzino A. Small increases in the level of Sox2 trigger the differentiation of mouse embryonic stem cells. Stem Cells. 2008;26:903–11.

    Article  CAS  PubMed  Google Scholar 

  78. Xu N, Papagiannakopoulos T, Pan G, Thomson JA, Kosik KS. MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell. 2009;137:647–58.

    Article  CAS  PubMed  Google Scholar 

  79. Takaya T, Ono K, Kawamura T, et al. MicroRNA-1 and MicroRNA-133 in spontaneous myocardial differentiation of mouse embryonic stem cells. Circ J. 2009;73:1492–7.

    Article  CAS  PubMed  Google Scholar 

  80. Sluijter JP, van Mil A, van Vliet P, et al. MicroRNA-1 and -499 regulate differentiation and proliferation in human-derived cardiomyocyte progenitor cells. Arterioscler Thromb Vasc Biol. 2010;30:859–68.

    Article  CAS  PubMed  Google Scholar 

  81. Ivey KN, Muth A, Arnold J, et al. MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell. 2008;2:219–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wilson KD, Hu S, Venkatasubrahmanyam S, et al. Dynamic microRNA expression programs during cardiac differentiation of human embryonic stem cells: role for miR-499. Circ Cardiovasc Genet. 2010;3:426–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chen F, Chen ZY, Yang HT. Expression profile of microRNAs in the cardiomyocytes derived from mouse embryonic stem cells. Sheng Li Xue Bao. 2014;66:702–8.

    CAS  PubMed  Google Scholar 

  84. Porrello ER, Mahmoud AI, Simpson E, et al. Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. Proc Natl Acad Sci U S A. 2013;110:187–92.

    Article  CAS  PubMed  Google Scholar 

  85. Chen JF, Mandel EM, Thomson JM, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2006;38:228–33.

    Article  CAS  PubMed  Google Scholar 

  86. Care A, Catalucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med. 2007;13:613–8.

    Article  CAS  PubMed  Google Scholar 

  87. Hosoda T, Zheng H, Cabral-da-Silva M, et al. Human cardiac stem cell differentiation is regulated by a mircrine mechanism. Circulation. 2011;123:1287–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Xiao J, Zhu X, He B, et al. MiR-204 regulates cardiomyocyte autophagy induced by ischemia-reperfusion through LC3-II. J Biomed Sci. 2011;18:35.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Crippa S, Cassano M, Messina G, et al. miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitors. J Cell Biol. 2011;193:1197–212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Arminan A, Gandia C, Bartual M, et al. Cardiac differentiation is driven by NKX2.5 and GATA4 nuclear translocation in tissue-specific mesenchymal stem cells. Stem Cells Dev. 2009;18:907–18.

    Article  CAS  PubMed  Google Scholar 

  91. Wang F, Gui YH. Progress in studies on microRNAs regulation of cardiac development. Zhonghua Er Ke Za Zhi. 2010;48:791–4.

    PubMed  Google Scholar 

  92. Glass C, Singla DK. MicroRNA-1 transfected embryonic stem cells enhance cardiac myocyte differentiation and inhibit apoptosis by modulating the PTEN/Akt pathway in the infarcted heart. Am J Physiol Heart Circ Physiol. 2011;301:H2038–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Glass C, Singla DK. ES cells overexpressing microRNA-1 attenuate apoptosis in the injured myocardium. Mol Cell Biochem. 2011;357:135–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Pisano F, Altomare C, Cervio E, et al. Combination of miRNA499 and miRNA133 exerts a synergic effect on cardiac differentiation. Stem Cells. 2015;33:1187–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Han JK, Chang SH, Cho HJ, et al. Direct conversion of adult skin fibroblasts to endothelial cells by defined factors. Circulation. 2014;130:1168–78.

    Article  CAS  PubMed  Google Scholar 

  96. Qian L, Berry EC, Fu JD, Ieda M, Srivastava D. Reprogramming of mouse fibroblasts into cardiomyocyte-like cells in vitro. Nat Protoc. 2013;8:1204–15.

    Article  PubMed  CAS  Google Scholar 

  97. Qian L, Huang Y, Spencer CI, et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature. 2012;485:593–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Song K, Nam YJ, Luo X, et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. 2012;485:599–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Nam YJ, Song K, Luo X, et al. Reprogramming of human fibroblasts toward a cardiac fate. Proc Natl Acad Sci U S A. 2013;110:5588–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Wada R, Muraoka N, Inagawa K, et al. Induction of human cardiomyocyte-like cells from fibroblasts by defined factors. Proc Natl Acad Sci U S A. 2013;110:12667–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Jayawardena TM, Egemnazarov B, Finch EA, et al. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res. 2012;110:1465–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Sadahiro T, Yamanaka S, Ieda M. Direct cardiac reprogramming: progress and challenges in basic biology and clinical applications. Circ Res. 2015;116:1378–91.

    Article  CAS  PubMed  Google Scholar 

  103. Eulalio A, Mano M, Dal Ferro M, et al. Functional screening identifies miRNAs inducing cardiac regeneration. Nature. 2012;492:376–81.

    Article  CAS  PubMed  Google Scholar 

  104. Huang J, Zhang Z, Guo J, et al. Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium. Circ Res. 2010;106:1753–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Tivnan A, Orr WS, Gubala V, et al. Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a using anti-disialoganglioside GD2 coated nanoparticles. PLoS One. 2012;7, e38129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Ibrahim AG, Cheng K, Marban E. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports. 2014;2:606–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Ghosh R, Singh LC, Shohet JM, Gunaratne PH. A gold nanoparticle platform for the delivery of functional microRNAs into cancer cells. Biomaterials. 2013;34:807–16.

    Article  CAS  PubMed  Google Scholar 

  108. Vasir JK, Labhasetwar V. Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev. 2007;59:718–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456:980–4.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Fondazione IRCCS Policlinico San Matteo Pavia, Italy; the Ministero Italiano dell’Università e della Ricerca (MIUR, 2010BWY8E9); the Ministero Italiano della Sanità (GR-2007-683466; GR-2008-1142781; GR-2010-2320533); the Fondazione Cariplo (2007-5984); and the Ministero Italiano degli Affari Esteri (Grant ZA11GR2).

We want to thank Laurene Kelly for help with editing the manuscript.

Author information

Authors and Affiliations

  1. Department of Molecular Medicine - Cardiology Unit, University of Pavia, Pavia, Italy

    Massimiliano Gnecchi & Riccardo Bariani

  2. Department of Cardiothoracic and Vascular Sciences - Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology, Institute of Research and Treatment Foundation Polyclinic San Matteo, Pavia, Italy

    Massimiliano Gnecchi & Federica Pisano

  3. Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Institute of Research and Treatment Foundation Polyclinic San Matteo, Pavia, Italy

    Massimiliano Gnecchi & Federica Pisano

  4. Department of Medicine, University of Cape Town, Cape Town, South Africa

    Massimiliano Gnecchi

Authors
  1. Massimiliano Gnecchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Federica Pisano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Riccardo Bariani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Massimiliano Gnecchi .

Editor information

Editors and Affiliations

  1. Columbia University Medical Center, New York, New York, USA

    Gaetano Santulli

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Gnecchi, M., Pisano, F., Bariani, R. (2015). microRNA and Cardiac Regeneration. In: Santulli, G. (eds) microRNA: Basic Science. Advances in Experimental Medicine and Biology, vol 887. Springer, Cham. https://doi.org/10.1007/978-3-319-22380-3_7

Download citation

Publish with us

Policies and ethics

Search

Navigation