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Derivation of a cardiopoietic population from human mesenchymal stem cells yields cardiac progeny


Stem cells have emerged as a next-generation therapy for cardiovascular disease. Initial clinical trials in patients with myocardial infarction document improved cardiac performance after administration of stem cells, translating their regenerative potential from the bench to the bedside. However, the promise of stem cell-based therapy has yet to be fully exploited, in part due to varying degrees of efficacy on follow-up. Contributing to the uncertain outcome is the variable cardiogenic potential of patient-derived stem cells. A strategy mimicking cardiogenic signaling was here formulated to transform mesenchymal stem cells, derived from human bone marrow, into cardiac progenitors. We identified a set of recombinant trophic factors capable of collectively inducing nuclear translocation of cardiac-specific transcription factors, engaging mesenchymal stem cells into cardiopoiesis, and ultimately securing a phenotype with functional excitation–contraction coupling. Maximizing the cardiogenic potential of human mesenchymal stem cells achieves a critical step in optimizing therapeutic translation.

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Figure 1: Cardiogenic potential of stem cells
Figure 2: Derivation of a cardiopoietic population from human mesenchymal stem cells yields functional progeny


  1. Anversa P and Nadal-Ginard B (2002) Myocyte renewal and ventricular remodelling. Nature 415: 240–243

    Article  CAS  Google Scholar 

  2. Towbin JA and Bowles NE (2002) The failing heart. Nature 415: 227–233

    Article  CAS  Google Scholar 

  3. Beltrami AP et al. (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114: 763–776

    Article  CAS  Google Scholar 

  4. Laugwitz KL et al. (2005) Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433: 647–653

    Article  CAS  Google Scholar 

  5. Dimmeler S et al. (2005) Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 115: 572–583

    Article  CAS  Google Scholar 

  6. Wollert KC and Drexler H (2005) Clinical applications of stem cells for the heart. Circ Res 96: 151–163

    Article  CAS  Google Scholar 

  7. Menasché P et al. (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 41: 1078–1083

    Article  Google Scholar 

  8. Schächinger V et al. (2004) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI trial. J Am Coll Cardiol 44: 1690–1699

    Article  Google Scholar 

  9. Wollert KC et al. (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364: 141–148

    Article  Google Scholar 

  10. Fernández-Avilés F et al. (2004) Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res 95: 742–748

    Article  Google Scholar 

  11. Perin EC et al. (2004) Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 110: II213–II218

    Article  Google Scholar 

  12. Gnecchi M et al. (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11: 367–368

    Article  CAS  Google Scholar 

  13. Fraidenraich D et al. (2004) Rescue of cardiac defects in Id knockout embryos by injection of embryonic stem cells. Science 306: 247–252

    Article  CAS  Google Scholar 

  14. Orlic D et al. (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410: 701–705

    Article  CAS  Google Scholar 

  15. Murry CE et al. (2004) Hematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428: 664–668

    Article  CAS  Google Scholar 

  16. Nygren JM et al. (2004) Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 10: 494–501

    Article  CAS  Google Scholar 

  17. Behfar A et al. (2002) Stem cell differentiation requires a paracrine pathway in the heart. FASEB J 16: 1558–1566

    Article  Google Scholar 

  18. Perez-Terzic C et al. (2003) Structural adaptation of the nuclear pore complex in stem cell-derived cardiomyocytes. Circ Res 92: 444–452

    Article  CAS  Google Scholar 

  19. Hodgson DM et al. (2004) Stable benefit of embryonic stem cell therapy in myocardial infarction. Am J Physiol 287: H471–H479

    CAS  Google Scholar 

  20. Foley A and Mercola M (2004) Heart induction: embryology to cardiomyocyte regeneration. Trends Cardiovasc Med 14: 121–125

    Article  CAS  Google Scholar 

  21. Jiang Y et al. (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418: 41–49

    Article  CAS  Google Scholar 

  22. Tomita S et al. (1999) Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100: II247–II256

    Article  CAS  Google Scholar 

  23. Koh SH et al. (2005) Co-culture of human CD34+ cells with mesenchymal stem cells increases the survival of CD34+ cells against the 5-aza-deoxycytidine- or trichostatin A-induced cell death. Biochem Biophys Res Commun 329: 1039–1045

    Article  CAS  Google Scholar 

  24. Behfar A et al. (2005) Administration of allogenic stem cells dosed to secure cardiogenesis and sustained infarct repair. Ann NY Acad Sci 1049: 189–198

    Article  Google Scholar 

  25. Olson EN and Schneider MD (2003) Sizing up the heart: development redux in disease. Genes Dev 17: 1937–1956

    Article  CAS  Google Scholar 

  26. Pittenger MF and Martin BJ (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 95: 9–20

    Article  CAS  Google Scholar 

  27. Hodgson DM et al. (2003) Cellular remodeling in heart failure disrupts KATP channel-dependent stress tolerance. EMBO J 22: 1732–1742

    Article  CAS  Google Scholar 

  28. Behfar A et al. (2004) Newly identified cardiopoietic stem cell population recruited by TNF-α from pluripotent embryonic cells [abstract]. Circulation 110: III-302

    Google Scholar 

  29. Behfar A et al. (2005) Guided cardiogenesis for safe stem cell-based therapy [abstract]. Clin Pharmacol Ther 77: P3

    Article  Google Scholar 

  30. Mummery C et al. (2003) Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. Circulation 107: 2733–2740

    Article  CAS  Google Scholar 

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We thank DL Mann and C Mummery for the generous gifts of TNF-α-transgenic mice and endodermal cells, RS Faustino and RB Dyer for expert assistance, and S Vuk-Pavlovic for guidance and discussion. This work was supported by the National Institutes of Health, the Marriott Heart Disease Research Program, the Marriott Foundation, the Ted Nash Long Life Foundation, the Ralph Wilson Medical Research Foundation, and the Miami Heart Research Institute.

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Correspondence to Andre Terzic.

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Behfar, A., Terzic, A. Derivation of a cardiopoietic population from human mesenchymal stem cells yields cardiac progeny. Nat Rev Cardiol 3 (Suppl 1), S78–S82 (2006).

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