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Resident progenitors and bone marrow stem cells in myocardial renewal and repair

Nature Clinical Practice Cardiovascular Medicine volume 3, pages S83–S89 (2006)Cite this article

Abstract

Although cardiac transplantation is still the treatment of choice for end-stage heart disease, the side effects derived from the use of immunosuppressants and the limited availability of donors have prompted the search for alternative therapeutic strategies. Among other possibilities, cell transplantation approaches have recently emerged as new alternatives to stimulate myocardial regeneration. These approaches are mainly based on the increasing number of reports documenting the plasticity of stem cells of various origins, particularly the ability of several types of embryonic and adult stem cells to give rise to cardiomyocytes. Unprecedented in the field of 'translational research' and based on the urgent need for alternative therapies, the promising results obtained with animal models have been quickly transferred to the clinical arena, where numerous small pilot studies using different cell types are already ongoing and/or have reported promising results. Nevertheless, the lack of randomization, the variability and small size of the treated cohorts and the use of mixed populations of cells have often clouded the significance and prevented a mechanistic interpretation of the results. Here, we briefly review the use of bone-marrow-derived and cardiac-derived stem/progenitor cells in myocardial regeneration studies and discuss their significance for the future of the field of myocardial regeneration.

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Figure 1: Mouse fetal liver stem cells can differentiate into cardiomyocytes in vivo

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References

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

    Article  CAS  Google Scholar 

  2. Nadal-Ginard B et al. (2003) Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res 92: 139–150

    Article  CAS  Google Scholar 

  3. Keller G (2005) Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev 19: 1129–1255

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Yoon YS et al. (2005) Myocardial regeneration with bone-marrow-derived stem cells. Biol Cell 97: 253–263

    Article  CAS  Google Scholar 

  6. Jackson KA et al. (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107: 1395–1402

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Orlic D et al. (2001) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 98: 10344–13049

    Article  CAS  Google Scholar 

  9. Balsam LB et al. (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428: 668–673

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. 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 

  12. Kajstura J et al. (2005) Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res 96: 127–137

    Article  CAS  Google Scholar 

  13. 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 

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

    Article  CAS  Google Scholar 

  15. Torella D et al. (2005) Cardiac stem and progenitor cell biology for regenerative medicine. Trends Cardiovasc Med 15: 229–236

    Article  CAS  Google Scholar 

  16. Yoon YS et al. (2005) Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest 115: 326–338

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  18. Oh H et al. (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci USA 100: 12313–12318

    Article  CAS  Google Scholar 

  19. Matsuura K et al. (2004) Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279: 11384–11391

    Article  CAS  Google Scholar 

  20. Martin CM et al. (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

    Article  CAS  Google Scholar 

  21. Messina E et al. (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95: 911–921

    Article  CAS  Google Scholar 

  22. Dawn B et al. (2005) Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci USA 102: 3766–3771

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  24. Quaini F et al. (2002) Chimerism of the transplanted heart. N Engl J Med 346: 5–15

    Article  Google Scholar 

  25. Bayes-Genis A et al. (2004) Cardiac chimerism in recipients of peripheral-blood and bone marrow stem cells. Eur J Heart Fail 6: 399–402

    Article  Google Scholar 

  26. Laflamme MA et al. (2002) Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human hearts. Circ Res 90: 634–640

    Article  CAS  Google Scholar 

  27. Agbulut O et al. (2003) Temporal patterns of bone marrow cell differentiation following transplantation in doxorubicin-induced cardiomyopathy. Cardiovasc Res 58: 451–459

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  29. Zhang S et al. (2004) Long-term effects of bone marrow mononuclear cell transplantation on left ventricular function and remodeling in rats. Life Sci 74: 2853–2864

    Article  CAS  Google Scholar 

  30. Fuchs S et al. (2001) Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. J Am Coll Cardiol 37: 1726–1732

    Article  CAS  Google Scholar 

  31. Kamihata H et al. (2001) Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation 104: 1046–1052

    Article  CAS  Google Scholar 

  32. Hamano K et al. (2002) Therapeutic angiogenesis induced by local autologous bone marrow cell implantation. Ann Thorac Surg 73: 1210–1215

    Article  Google Scholar 

  33. Bel A et al. (2003) Transplantation of autologous fresh bone marrow into infarcted myocardium: a word of caution. Circulation 108 (Suppl 1): II247–II252

    PubMed  Google Scholar 

  34. Makino S et al. (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103: 697–705

    Article  CAS  Google Scholar 

  35. Fukuda K (2001) Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineering. Artif Organs 25: 187–193

    Article  CAS  Google Scholar 

  36. Fukuhara S et al. (2003) Direct cell–cell interaction of cardiomyocytes is key for bone marrow stromal cells to go into cardiac lineage in vitro. J Thorac Cardiovasc Surg 125: 1470–1480

    Article  Google Scholar 

  37. Saito T et al. (2002) Xenotransplant cardiac chimera: immune tolerance of adult stem cells. Ann Thorac Surg 74: 19–24

    Article  Google Scholar 

  38. Wang JS et al. (2000) Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages. J Thorac Cardiovasc Surg 120: 999–1005

    Article  CAS  Google Scholar 

  39. Wang JS et al. (2001) The coronary delivery of marrow stromal cells for myocardial regeneration: pathophysiologic and therapeutic implications. J Thorac Cardiovasc Surg 122: 699–705

    Article  CAS  Google Scholar 

  40. Saito T et al. (2003) Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction. J Thorac Cardiovasc Surg 126: 114–123

    Article  Google Scholar 

  41. Duan HF et al. (2003) Treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor. Mol Ther 8: 467–474

    Article  CAS  Google Scholar 

  42. Mangi AA et al. (2003) Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 9: 1195–1201

    Article  CAS  Google Scholar 

  43. Davani S et al. (2003) Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a rat cellular cardiomyoplasty model. Circulation 108 (Suppl 1): II253–II258

    PubMed  Google Scholar 

  44. Tang YL et al. (2004) Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul Pept 117: 3–10

    Article  CAS  Google Scholar 

  45. Shake JG et al. (2002) Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg 73: 1919–1926

    Article  Google Scholar 

  46. Tomita S et al. (2002) Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg 123: 1132–1140

    Article  Google Scholar 

  47. Yau TM et al. (2003) Beneficial effect of autologous cell transplantation on infarcted heart function: comparison between bone marrow stromal cells and heart cells. Ann Thorac Surg 75: 169–177

    Article  Google Scholar 

  48. Oswald J et al. (2004) Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 22: 377–384

    Article  Google Scholar 

  49. Toma C et al. (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105: 93–98

    Article  Google Scholar 

  50. Min JY et al. (2002) Significant improvement of heart function by cotransplantation of human mesenchymal stem cells and fetal cardiomyocytes in postinfarcted pigs. Ann Thorac Surg 74: 1568–1575

    Article  Google Scholar 

  51. Airey JA et al. (2004) Human mesenchymal stem cells form Purkinje fibers in fetal sheep heart. Circulation 109: 1401–1407

    Article  Google Scholar 

  52. Kawamoto A et al. (2003) Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation 107: 461–468

    Article  Google Scholar 

  53. Kawamoto A et al. (2001) Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 103: 634–637

    Article  CAS  Google Scholar 

  54. Kocher AA et al. (2001) Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 7: 430–436

    Article  CAS  Google Scholar 

  55. Eisenberg LM et al. (2003) Hematopoietic cells from bone marrow have the potential to differentiate into cardiomyocytes in vitro. Anat Rec A Discov Mol Cell Evol Biol 274: 870–882

    Article  Google Scholar 

  56. Kudo M et al. (2003) Implantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart. J Mol Cell Cardiol 35: 1113–1119

    Article  CAS  Google Scholar 

  57. Hamano K et al. (2001) Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J 65: 845–847

    Article  CAS  Google Scholar 

  58. Strauer BE et al. (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106: 1913–1918

    Article  Google Scholar 

  59. Perin EC et al. (2003) Transendocardial, autologous bone marrow cell transplantation for severe chronic ischemic heart failure. Circulation 107: 2294–2302

    Article  Google Scholar 

  60. Assmus B et al. (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE–AMI). Circulation 106: 3009–3017

    Article  Google Scholar 

  61. Tse HF et al. (2003) Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 361: 47–49

    Article  Google Scholar 

  62. Fuchs S et al. (2003) Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol 41: 1721–1724

    Article  Google Scholar 

  63. 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 

  64. Galinanes M et al. (2004) Autotransplantation of unmanipulated bone marrow into scarred myocardium is safe and enhances cardiac function in humans. Cell Transplant 13: 7–13

    Article  Google Scholar 

  65. Stamm C et al. (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361: 45–46

    Article  Google Scholar 

  66. Stamm C et al. (2004) CABG and bone marrow stem cell transplantation after myocardial infarction. Thorac Cardiovasc Surg 52: 152–158

    Article  CAS  Google Scholar 

  67. Kang HJ et al. (2004) Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet 363: 751–756

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Postdoctoral Fellows, Cardiovascular Institute and Center for Cardiovascular Health, Mount Sinai School of Medicine, New York, NY, USA

    Simón Méndez-Ferrer & Georgina M Ellison

  2. Senior Investigator at the Cardiovascular Institute and Center for Cardiovascular Health, Mount Sinai School of Medicine, New York, NY, USA

    Bernardo Nadal-Ginard

  3. a Postdoctoral Fellow in the Laboratory of Cellular and Molecular Exercise Physiology, at Liverpool John Moores University, Liverpool, UK

    Georgina M Ellison

  4. Assistant Professor of Cardiology in the Department of Experimental and Clinical Medicine, Laboratory of Molecular and Cellular Cardiology, at Magna Graecia University, Catanzaro, Italy

    Daniele Torella

Authors
  1. Simón Méndez-Ferrer
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  2. Georgina M Ellison
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  4. Bernardo Nadal-Ginard
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Correspondence to Bernardo Nadal-Ginard.

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Méndez-Ferrer, S., Ellison, G., Torella, D. et al. Resident progenitors and bone marrow stem cells in myocardial renewal and repair. Nat Rev Cardiol 3 (Suppl 1), S83–S89 (2006). https://doi.org/10.1038/ncpcardio0415

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  • DOI: https://doi.org/10.1038/ncpcardio0415

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