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Stem Cell Therapy: Promising Treatment in Heart Failure?

  • Nonpharmacologic Therapy: Surgery, Ventricular Assist Devices, Biventricular Pacing, and Exercise (AK Hasan, Section Editor)
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Abstract

Cardiac repair through the use of regenerative medicine has been a considerable research focus over the last decade. Several stem cell types have been investigated over this timeframe as potential candidates to target post-infarction heart failure. The progression of investigation through the rigors of clinical trial design has provided some answers as to the potential clinical utility of this therapy; although there are many questions that remain. This review will concentrate on the clinical trial results of stem cell therapy for cardiac repair since the turn of the century and discuss some of the points that need clarification before this form of therapy can be considered for widespread applicability.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Roger VL, et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–220. Updated statistics regarding heart failure in the US, outlining the growing burden of this disease process in the US.

    Article  PubMed  Google Scholar 

  2. Avery CL, et al. The population burden of heart failure attributable to modifiable risk factors: the ARIC (Atherosclerosis Risk in Communities) study. J Am Coll Cardiol. 2012;60(17):1640–6.

    Article  PubMed  Google Scholar 

  3. Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. 1990;81(4):1161–72.

    Article  PubMed  CAS  Google Scholar 

  4. McMurray JJV, Pfeffer MA. Heart failure. Lancet. 2005;365(9474):1877–89.

    Article  PubMed  Google Scholar 

  5. Titler MG, et al. Cost of hospital care for older adults with heart failure: medical, pharmaceutical, and nursing costs. Health Serv Res. 2008;43(2):635–55.

    Article  PubMed  Google Scholar 

  6. •• Menasche P, et al. Autologous skeletal myoblast transplantation for cardiac insufficiency. First clinical case. Arch Mal Coeur Vaiss. 2001;94(3):180–2. First ever report of stem cell therapy for cardiac repair.

    PubMed  CAS  Google Scholar 

  7. Menasche P, et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol. 2003;41(7):1078–83.

    Article  PubMed  Google Scholar 

  8. Menasche P, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation. 2008;117(9):1189–200.

    Article  PubMed  Google Scholar 

  9. Duckers HJ, et al. Final results of a phase IIa, randomised, open-label trial to evaluate the percutaneous intramyocardial transplantation of autologous skeletal myoblasts in congestive heart failure patients: the SEISMIC trial. EuroIntervention. 2011;6(7):805–12.

    Article  PubMed  Google Scholar 

  10. •• Strauer BE, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002;106(15):1913–8. First ever clinical trial of stem cell therapy for cardiac repair.

    Article  PubMed  Google Scholar 

  11. Assmus B, et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation. 2002;106(24):3009–17.

    Article  PubMed  Google Scholar 

  12. Wollert KC, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004;364(9429):141–8.

    Article  PubMed  Google Scholar 

  13. Schachinger V, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006;355(12):1210–21.

    Article  PubMed  CAS  Google Scholar 

  14. Lunde K, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006;355(12):1199–209.

    Article  PubMed  CAS  Google Scholar 

  15. Meyer GP, et al. 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. 2006;113(10):1287–94.

    Article  PubMed  Google Scholar 

  16. Traverse JH, et al. 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. 2012;308(22):2380–9.

    Google Scholar 

  17. Surder D, et al. Cell-based therapy for myocardial repair in patients with acute myocardial infarction: rationale and study design of the SWiss multicenter Intracoronary Stem cells Study in Acute Myocardial Infarction (SWISS-AMI). Am Heart J. 2010;160(1):58–64.

    Article  PubMed  Google Scholar 

  18. Traverse JH, et al. 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. 2011;306(19):2110–9.

    Article  PubMed  CAS  Google Scholar 

  19. • Abdel-Latif A, et al. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007;167(10):989–97. First meta-analysis to describe overall benefit of BMC in the setting of acute MI.

    Article  PubMed  Google Scholar 

  20. Strauer BE, et al. Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. J Am Coll Cardiol. 2005;46(9):1651–8.

    Article  PubMed  Google Scholar 

  21. Strauer BE, Yousef M, Schannwell CM. The acute and long-term effects of intracoronary Stem cell Transplantation in 191 patients with chronic heARt failure: the STAR-heart study. Eur J Heart Fail. 2010;12(7):721–9.

    Article  PubMed  Google Scholar 

  22. Assmus B, et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med. 2006;355(12):1222–32.

    Article  PubMed  CAS  Google Scholar 

  23. Perin EC, et al. 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. 2012;307(16):1717–26.

    Article  PubMed  CAS  Google Scholar 

  24. Dominici M, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7.

    Article  PubMed  CAS  Google Scholar 

  25. Heng TS, et al. Stem cells–meet immunity. J Mol Med (Berl). 2009;87(11):1061–9.

    Article  Google Scholar 

  26. El-Badri NS, Maheshwari A, Sanberg PR. Mesenchymal stem cells in autoimmune disease. Stem Cells Dev. 2004;13(5):463–72.

    Article  PubMed  Google Scholar 

  27. Chen SL, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol. 2004;94(1):92–5.

    Article  PubMed  Google Scholar 

  28. Florenzano F, Minguell JJ. Autologous mesenchymal stem cell transplantation after acute myocardial infarction. Am J Cardiol. 2005;95(3):435.

    Article  PubMed  Google Scholar 

  29. Katritsis DG, et al. Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheter Cardiovasc Interv. 2005;65(3):321–9.

    Article  PubMed  Google Scholar 

  30. Chen S, et al. Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery. J Invasive Cardiol. 2006;18(11):552–6.

    PubMed  Google Scholar 

  31. Lo R, Hsia HH. Ventricular arrhythmias in heart failure patients. Cardiol Clin. 2008;26(3):381–403. vi.

    Article  PubMed  Google Scholar 

  32. Katritsis DG, et al. Electrophysiological effects of intracoronary transplantation of autologous mesenchymal and endothelial progenitor cells. Europace. 2007;9(3):167–71.

    Article  PubMed  Google Scholar 

  33. Hare JM, et al. 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. 2012;308(22):2369–79.

    Google Scholar 

  34. Trachtenberg B, et al. Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: a randomized, double-blind, placebo-controlled study of safety and efficacy. Am Heart J. 2011;161(3):487–93.

    Article  PubMed  CAS  Google Scholar 

  35. Bartunek J, et al. C-Cure multicenter triall: lineage specified bone marrow derived cardiopoietic mesenchymal stem cells for treatment of ischemic cardiomyopathy. J Am Coll Cardiol. 2011;57:E200.

    Article  Google Scholar 

  36. Beltrami AP, et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med. 2001;344(23):1750–7.

    Article  PubMed  CAS  Google Scholar 

  37. Quaini F, et al. Chimerism of the transplanted heart. N Engl J Med. 2002;346(1):5–15.

    Article  PubMed  Google Scholar 

  38. Bergmann O, et al. Evidence for cardiomyocyte renewal in humans. Science. 2009;324(5923):98–102.

    Article  PubMed  CAS  Google Scholar 

  39. •• Beltrami AP, Beltrami AP, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114(6):763–76. First report of the discovery of endogenous stem cells recovered from the mammalian heart.

    Article  PubMed  CAS  Google Scholar 

  40. Messina E, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res. 2004;95(9):911–21.

    Article  PubMed  CAS  Google Scholar 

  41. •• Bolli R, et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet. 2011;378(9806):1847–57. First in-human clinical trial of CSC for the treatment of post-infarction left ventricular dysfunction.

    Article  PubMed  Google Scholar 

  42. Chugh AR, et al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation. 2012;126(11 Suppl 1):S54–64.

    Article  PubMed  CAS  Google Scholar 

  43. •• Makkar RR, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet. 2012;379(9819):895–904. First clinical trial investigating the use of CDC for the treatment of ischemic heart disease.

    Article  PubMed  Google Scholar 

  44. Cheng K, et al. Magnetic enhancement of cell retention, engraftment and functional benefit after intracoronary delivery of cardiac-derived stem cells in a rat model of ischemia/reperfusion. Cell Transplant. 2012;21(6):1121–35.

    Google Scholar 

  45. Terrovitis J, et al. Noninvasive quantification and optimization of acute cell retention by in vivo positron emission tomography after intramyocardial cardiac-derived stem cell delivery. J Am Coll Cardiol. 2009;54(17):1619–26.

    Article  PubMed  Google Scholar 

  46. Freyman T, et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J. 2006;27(9):1114–22.

    Article  PubMed  Google Scholar 

  47. Frangogiannis NG. The stromal cell-derived factor-1/CXCR4 axis in cardiac injury and repair. J Am Coll Cardiol. 2011;58(23):2424–6.

    Article  PubMed  Google Scholar 

  48. Martin-Rendon E, et al. Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review. Eur Heart J. 2008;29(15):1807–18.

    Article  PubMed  CAS  Google Scholar 

  49. Kutschka I, et al. Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts. Circulation. 2006;114(1 Suppl):I167–73.

    PubMed  Google Scholar 

  50. Memon IA, et al. Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets. J Thorac Cardiovasc Surg. 2005;130(5):1333–41.

    Article  PubMed  Google Scholar 

  51. Christman KL, et al. Injectable fibrin scaffold improves cell transplant survival, reduces infarct expansion, and induces neovasculature formation in ischemic myocardium. J Am Coll Cardiol. 2004;44(3):654–60.

    Article  PubMed  CAS  Google Scholar 

  52. Suzuki K, et al. Heat shock treatment enhances graft cell survival in skeletal myoblast transplantation to the heart. Circulation. 2000;102(19 Suppl 3):III216–21.

    PubMed  CAS  Google Scholar 

  53. Laflamme MA, et al. Formation of human myocardium in the rat heart from human embryonic stem cells. Am J Pathol. 2005;167(3):663–71.

    Article  PubMed  CAS  Google Scholar 

  54. Niagara MI, et al. Pharmacologically preconditioned skeletal myoblasts are resistant to oxidative stress and promote angiomyogenesis via release of paracrine factors in the infarcted heart. Circ Res. 2007;100(4):545–55.

    Article  PubMed  CAS  Google Scholar 

  55. Pasha Z, et al. Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. Cardiovasc Res. 2008;77(1):134–42.

    Article  PubMed  CAS  Google Scholar 

  56. Pons J, et al. VEGF improves survival of mesenchymal stem cells in infarcted hearts. Biochem Biophys Res Commun. 2008;376(2):419–22.

    Article  PubMed  CAS  Google Scholar 

  57. Barbash IM, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation. 2003;108(7):863–8.

    Article  PubMed  Google Scholar 

  58. Gupta R, Losordo DW. Challenges in the translation of cardiovascular cell therapy. J Nucl Med. 2010;51 Suppl 1:122S–7.

    Article  PubMed  Google Scholar 

  59. Flett AS, et al. Evaluation of techniques for the quantification of myocardial scar of differing etiology using cardiac magnetic resonance. JACC Cardiovasc Imaging. 2011;4(2):150–6.

    Article  PubMed  Google Scholar 

  60. Hung J, et al. Cardiac image modeling tool for quantitative analysis of global and regional cardiac wall motion. Invest Radiol. 2009;44(5):271–8.

    Article  PubMed  Google Scholar 

  61. Hulten EA, et al. Stress CT perfusion: coupling coronary anatomy with physiology. J Nucl Cardiol. 2012;19(3):588–600.

    Article  PubMed  Google Scholar 

  62. Morton G, et al. Quantitative cardiovascular magnetic resonance perfusion imaging: inter-study reproducibility. Eur Heart J Cardiovasc Imaging. 2012;13(11):954–60.

    Article  PubMed  Google Scholar 

  63. Haas F, et al. Preoperative positron emission tomographic viability assessment and perioperative and postoperative risk in patients with advanced ischemic heart disease. J Am Coll Cardiol. 1997;30(7):1693–700.

    Article  PubMed  CAS  Google Scholar 

  64. Baer FM, et al. Comparison of low-dose dobutamine-gradient-echo magnetic resonance imaging and positron emission tomography with [18F]fluorodeoxyglucose in patients with chronic coronary artery disease. A functional and morphological approach to the detection of residual myocardial viability. Circulation. 1995;91(4):1006–15.

    Article  PubMed  CAS  Google Scholar 

  65. Tillisch J, et al. Reversibility of cardiac wall-motion abnormalities predicted by positron tomography. N Engl J Med. 1986;314(14):884–8.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, University of Louisville, 550 S Jackson Street ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA

    John H. Loughran, Atul R. Chugh & Roberto Bolli

  2. The School of Medicine, University of Louisville, Louisville, KY, USA

    Imtiaz Ismail

Authors
  1. John H. Loughran
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  2. Atul R. Chugh
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  3. Imtiaz Ismail
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  4. Roberto Bolli
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Correspondence to John H. Loughran.

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Loughran, J.H., Chugh, A.R., Ismail, I. et al. Stem Cell Therapy: Promising Treatment in Heart Failure?. Curr Heart Fail Rep 10, 73–80 (2013). https://doi.org/10.1007/s11897-012-0128-2

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