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Clinical Trials of Cardiac Repair with Adult Bone Marrow- Derived Cells

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Cellular Cardiomyoplasty

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1036))

Abstract

The past decade has witnessed a marked increase in the number of clinical trials of cardiac repair with adult bone marrow cells (BMCs). These trials included patients with acute myocardial infarction (MI) as well as chronic ischemic heart disease (IHD) and utilized different types of BMCs with variable numbers, routes of administration, and timings after MI. Given these differences in methods, the outcomes from these trials have been often disparate and controversial. However, analysis of pooled data suggests that BMC injection enhances left ventricular function, reduces infarct scar size, and improves remodeling in patients with acute MI as well as chronic IHD. BMC therapy also improves clinical outcomes during follow-up without any increase in adverse effects. Although the underlying mechanisms of heart repair are difficult to elucidate in human studies, valuable insights may be gleaned from subgroup analysis of key variables. This information may be utilized to design future randomized controlled trials to carefully determine the long-term safety and benefits of BMC therapy.

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References

  1. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB et al (2012) Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation 125:e2–e220

    Article  PubMed  Google Scholar 

  2. Pfeffer MA, Braunwald E (1990) Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation 81:1161–1172

    Article  PubMed  CAS  Google Scholar 

  3. Pfeffer MA, Pfeffer JM, Lamas GA (1993) Development and prevention of congestive heart failure following myocardial infarction. Circulation 87:IV120–IV125

    PubMed  CAS  Google Scholar 

  4. Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA et al (2007) Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med 167:989–997

    Article  PubMed  Google Scholar 

  5. Jeevanantham V, Butler M, Saad A, Abdel-Latif A, Zuba-Surma EK, Dawn B (2012) Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis. Circulation 126:551–568

    Article  PubMed  Google Scholar 

  6. Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S (2007) Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction. Eur Heart J 28: 766–772

    Article  PubMed  Google Scholar 

  7. Dawn B, Bolli R (2007) Bone marrow for cardiac repair: the importance of characterizing the phenotype and function of injected cells. Eur Heart J 28:651–652

    Article  PubMed  Google Scholar 

  8. Lipinski MJ, Biondi-Zoccai GG, Abbate A, Khianey R, Sheiban I, Bartunek J et al (2007) Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol 50:1761–1767

    Article  PubMed  Google Scholar 

  9. Hristov M, Heussen N, Schober A, Weber C (2006) Intracoronary infusion of autologous bone marrow cells and left ventricular function after acute myocardial infarction: a meta-analysis. J Cell Mol Med 10:727–733

    Article  PubMed  CAS  Google Scholar 

  10. Ellis WM, Georgiou GM, Roberton DM, Johnson GR (1984) The use of discontinuous Percoll gradients to separate populations of cells from human bone marrow and peripheral blood. J Immunol Methods 66:9–16

    Article  PubMed  CAS  Google Scholar 

  11. Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74

    Article  PubMed  CAS  Google Scholar 

  12. Spangrude GJ, Heimfeld S, Weissman IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62

    Article  PubMed  CAS  Google Scholar 

  13. Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183:1797–1806

    Article  PubMed  CAS  Google Scholar 

  14. Kucia M, Reca R, Campbell FR, Zuba-Surma E, Majka M, Ratajczak J et al (2006) A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+ stem cells identified in adult bone marrow. Leukemia 20:857–869

    Article  PubMed  CAS  Google Scholar 

  15. Zuba-Surma EK, Kucia M, Abdel-Latif A, Dawn B, Hall B, Singh R et al (2008) Morphological characterization of very small embryonic-like stem cells (VSELs) by ImageStream system analysis. J Cell Mol Med 12:292–303

    Article  PubMed  Google Scholar 

  16. Zuba-Surma EK, Kucia M, Dawn B, Guo Y, Ratajczak MZ, Bolli R (2008) Bone marrow-derived pluripotent very small embryonic-like stem cells (VSELs) are mobilized after acute myocardial infarction. J Mol Cell Cardiol 44:865–873

    Article  PubMed  CAS  Google Scholar 

  17. Zuba-Surma EK, Wojakowski W, Ratajczak MZ, Dawn B (2011) Very small embryonic-like stem cells: biology and therapeutic potential for heart repair. Antioxid Redox Signal 15:1821–1834

    Article  PubMed  CAS  Google Scholar 

  18. Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV et al (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913–1918

    Article  PubMed  Google Scholar 

  19. Penicka M, Horak J, Kobylka P, Pytlik R, Kozak T, Belohlavek O et al (2007) Intracoronary injection of autologous bone marrow-derived mononuclear cells in patients with large anterior acute myocardial infarction: a prematurely terminated randomized study. J Am Coll Cardiol 49:2373–2374

    Article  PubMed  Google Scholar 

  20. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT et al (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107:2294–2302

    Article  PubMed  Google Scholar 

  21. Karpov RS, Popov SV, Markov VA, Suslova TE, Ryabov VV, Poponina YS et al (2005) Autologous mononuclear bone marrow cells during reparative regeneration after acute myocardial infarction. Bull Exp Biol Med 140:640–643

    Article  PubMed  CAS  Google Scholar 

  22. Meluzin J, Mayer J, Groch L, Janousek S, Hornacek I, Hlinomaz O et al (2006) Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: the effect of the dose of transplanted cells on myocardial function. Am Heart J 152:975.e9–15

    Article  Google Scholar 

  23. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Silva GV 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  PubMed  Google Scholar 

  24. Strauer BE, Brehm M, Zeus T, Bartsch T, Schannwell C, Antke C et al (2005) 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 46:1651–1658

    Article  PubMed  Google Scholar 

  25. Ge J, Li Y, Qian J, Shi J, Wang Q, Niu Y et al (2006) Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI). Heart 92:1764–1767

    Article  PubMed  CAS  Google Scholar 

  26. Hendrikx M, Hensen K, Clijsters C, Jongen H, Koninckx R, Bijnens E et al (2006) Recovery of regional but not global contractile function by the direct intramyocardial autologous bone marrow transplantation: results from a randomized controlled clinical trial. Circulation 114:I101–I107

    Article  PubMed  Google Scholar 

  27. Mocini D, Staibano M, Mele L, Giannantoni P, Menichella G, Colivicchi F et al (2006) Autologous bone marrow mononuclear cell transplantation in patients undergoing coronary artery bypass grafting. Am Heart J 151:192–197

    Article  PubMed  Google Scholar 

  28. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H et al (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355:1210–1221

    Article  PubMed  CAS  Google Scholar 

  29. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T et al (2006) Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 355:1199–1209

    Article  PubMed  CAS  Google Scholar 

  30. Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R et al (2006) Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 355:1222–1232

    Article  PubMed  CAS  Google Scholar 

  31. Tse HF, Thambar S, Kwong YL, Rowlings P, Bellamy G, McCrohon J et al (2007) Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial). Eur Heart J 28:2998–3005

    Article  PubMed  Google Scholar 

  32. Huikuri HV, Kervinen K, Niemela M, Ylitalo K, Saily M, Koistinen P et al (2008) Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction. Eur Heart J 29:2723–2732

    Article  PubMed  Google Scholar 

  33. Cao F, Sun D, Li C, Narsinh K, Zhao L, Li X et al (2009) Long-term myocardial functional improvement after autologous bone marrow mononuclear cells transplantation in patients with ST-segment elevation myocardial infarction: 4 years follow-up. Eur Heart J 30:1986–1994

    Article  PubMed  Google Scholar 

  34. Lipiec P, Krzeminska-Pakula M, Plewka M, Kusmierek J, Plachcinska A, Szuminski R et al (2009) Impact of intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction on left ventricular perfusion and function: a 6-month follow-up gated 99mTc-MIBI single-photon emission computed tomography study. Eur J Nucl Med Mol Imaging 36:587–593

    Article  PubMed  Google Scholar 

  35. Tendera M, Wojakowski W, Ruzyllo W, Chojnowska L, Kepka C, Tracz W et al (2009) Intracoronary infusion of bone marrow-derived selected CD34 + CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. Eur Heart J 30:1313–1321

    Article  PubMed  Google Scholar 

  36. Wohrle J, Merkle N, Mailander V, Nusser T, Schauwecker P, von Scheidt F et al (2010) Results of intracoronary stem cell therapy after acute myocardial infarction. Am J Cardiol 105:804–812

    Article  PubMed  CAS  Google Scholar 

  37. Traverse JH, McKenna DH, Harvey K, Jorgenso BC, Olson RE, Bostrom N et al (2010) Results of a phase 1, randomized, double-blind, placebo-controlled trial of bone marrow mononuclear stem cell administration in patients following ST-elevation myocardial infarction. Am Heart J 160:428–434

    Article  PubMed  Google Scholar 

  38. van Ramshorst J, Bax JJ, Beeres SL, Dibbets-Schneider P, Roes SD, Stokkel MP et al (2009) Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA 301:1997–2004

    Article  PubMed  Google Scholar 

  39. Pokushalov E, Romanov A, Chernyavsky A, Larionov P, Terekhov I, Artyomenko S et al (2010) Efficiency of intramyocardial injections of autologous bone marrow mononuclear cells in patients with ischemic heart failure: a randomized study. J Cardiovasc Transl Res 3:160–168

    Article  PubMed  Google Scholar 

  40. Strauer BE, Yousef M, Schannwell CM (2010) 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 12:721–729

    Article  PubMed  Google Scholar 

  41. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C et al (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364:141–148

    Article  PubMed  Google Scholar 

  42. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S et al (2006) 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 113:1287–1294

    Article  PubMed  Google Scholar 

  43. Schaefer A, Meyer GP, Fuchs M, Klein G, Kaplan M, Wollert KC et al (2006) Impact of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: results from the BOOST trial. Eur Heart J 27:929–935

    Article  PubMed  Google Scholar 

  44. Ruan W, Pan CZ, Huang GQ, Li YL, Ge JB, Shu XH (2005) Assessment of left ventricular segmental function after autologous bone marrow stem cells transplantation in patients with acute myocardial infarction by tissue tracking and strain imaging. Chin Med J (Engl) 118:1175–1181

    Google Scholar 

  45. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  46. Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J et al (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103:697–705

    Article  PubMed  CAS  Google Scholar 

  47. Hattan N, Kawaguchi H, Ando K, Kuwabara E, Fujita J, Murata M et al (2005) Purified cardiomyocytes from bone marrow mesenchymal stem cells produce stable intracardiac grafts in mice. Cardiovasc Res 65:334–344

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  49. Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ et al (2004) Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 94:92–95

    Article  PubMed  Google Scholar 

  50. Chen S, Liu Z, Tian N, Zhang J, Yei F, Duan B et al (2006) Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery. J Invasive Cardiol 18:552–556

    PubMed  Google Scholar 

  51. Katritsis DG, Sotiropoulou PA, Karvouni E, Karabinos I, Korovesis S, Perez SA et al (2005) Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheter Cardiovasc Interv 65:321–329

    Article  PubMed  Google Scholar 

  52. Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP et al (2009) A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 54:2277–2286

    Article  PubMed  CAS  Google Scholar 

  53. Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY et al (2012) 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 308:2369–2379

    PubMed  CAS  Google Scholar 

  54. Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M et al (2000) Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 95:952–958

    PubMed  CAS  Google Scholar 

  55. Bhatia M (2001) AC133 expression in human stem cells. Leukemia 15:1685–1688

    Article  PubMed  CAS  Google Scholar 

  56. Bartunek J, Vanderheyden M, Vandekerckhove B, Mansour S, De Bruyne B, De Bondt P et al (2005) Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety. Circulation 112:I178–I183

    PubMed  Google Scholar 

  57. Mansour S, Vanderheyden M, De Bruyne B, Vandekerckhove B, Delrue L, Van Haute I et al (2006) Intracoronary delivery of hematopoietic bone marrow stem cells and luminal loss of the infarct-related artery in patients with recent myocardial infarction. J Am Coll Cardiol 47:1727–1730

    Article  PubMed  Google Scholar 

  58. Colombo A, Castellani M, Piccaluga E, Pusineri E, Palatresi S, Longari V et al (2011) Myocardial blood flow and infarct size after CD133+ cell injection in large myocardial infarction with good recanalization and poor reperfusion: results from a randomized controlled trial. J Cardiovasc Med (Hagerstown) 12:239–248

    Article  Google Scholar 

  59. Manginas A, Goussetis E, Koutelou M, Karatasakis G, Peristeri I, Theodorakos A et al (2007) Pilot study to evaluate the safety and feasibility of intracoronary CD133(+) and CD133(-) CD34(+) cell therapy in patients with nonviable anterior myocardial infarction. Catheter Cardiovasc Interv 69:773–781

    Article  PubMed  Google Scholar 

  60. Stamm C, Kleine HD, Choi YH, Dunkelmann S, Lauffs JA, Lorenzen B et al (2007) Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J Thorac Cardiovasc Surg 133:717–725

    Article  PubMed  Google Scholar 

  61. Yerebakan C, Kaminski A, Westphal B, Donndorf P, Glass A, Liebold A et al (2011) Impact of preoperative left ventricular function and time from infarction on the long-term benefits after intramyocardial CD133(+) bone marrow stem cell transplant. J Thorac Cardiovasc Surg 142:1530–1539.e3

    Article  PubMed  Google Scholar 

  62. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N et al (2002) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 106:3009–3017

    Article  PubMed  Google Scholar 

  63. Britten MB, Abolmaali ND, Assmus B, Lehmann R, Honold J, Schmitt J et al (2003) Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation 108:2212–2218

    Article  PubMed  CAS  Google Scholar 

  64. Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C 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  PubMed  Google Scholar 

  65. Erbs S, Linke A, Adams V, Lenk K, Thiele H, Diederich KW et al (2005) Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study. Circ Res 97:756–762

    Article  PubMed  CAS  Google Scholar 

  66. Asahara T, Kawamoto A (2004) Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol 287:C572–C579

    Article  PubMed  CAS  Google Scholar 

  67. Kawamoto A, Tkebuchava T, Yamaguchi J, Nishimura H, Yoon YS, Milliken C et al (2003) Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation 107:461–468

    Article  PubMed  Google Scholar 

  68. Losordo DW, Schatz RA, White CJ, Udelson JE, Veereshwarayya V, Durgin M et al (2007) Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 115:3165–3172

    Article  PubMed  Google Scholar 

  69. Losordo DW, Henry TD, Davidson C, Sup Lee J, Costa MA, Bass T et al (2011) Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res 109:428–436

    Article  PubMed  CAS  Google Scholar 

  70. Kang HJ, Kim HS, Zhang SY, Park KW, Cho HJ, Koo BK 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  PubMed  CAS  Google Scholar 

  71. Kang HJ, Lee HY, Na SH, Chang SA, Park KW, Kim HK et al (2006) Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial. Circulation 114:I145–I151

    PubMed  Google Scholar 

  72. Li ZQ, Zhang M, Jing YZ, Zhang WW, Liu Y, Cui LJ et al (2007) The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). Int J Cardiol 115:52–56

    Article  PubMed  Google Scholar 

  73. Choi JH, Choi J, Lee WS, Rhee I, Lee SC, Gwon HC et al (2007) Lack of additional benefit of intracoronary transplantation of autologous peripheral blood stem cell in patients with acute myocardial infarction. Circ J 71:486–494

    Article  PubMed  Google Scholar 

  74. Tatsumi T, Ashihara E, Yasui T, Matsunaga S, Kido A, Sasada Y et al (2007) Intracoronary transplantation of non-expanded peripheral blood-derived mononuclear cells promotes improvement of cardiac function in patients with acute myocardial infarction. Circ J 71:1199–1207

    Article  PubMed  Google Scholar 

  75. Rosenzweig A (2006) Cardiac cell therapy–mixed results from mixed cells. N Engl J Med 355:1274–1277

    Article  PubMed  CAS  Google Scholar 

  76. Martin-Rendon E, Brunskill SJ, Hyde CJ, Stanworth SJ, Mathur A, Watt SM (2008) Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review. Eur Heart J 29:1807–1818

    Article  PubMed  CAS  Google Scholar 

  77. Zhang SN, Sun AJ, Ge JB, Yao K, Huang ZY, Wang KQ et al (2009) Intracoronary autologous bone marrow stem cells transfer for patients with acute myocardial infarction: a meta-analysis of randomised controlled trials. Int J Cardiol 136:178–185

    Article  PubMed  Google Scholar 

  78. Piepoli MF, Vallisa D, Arbasi M, Cavanna L, Cerri L, Mori M et al (2010) Bone marrow cell transplantation improves cardiac, autonomic, and functional indexes in acute anterior myocardial infarction patients (Cardiac Study). Eur J Heart Fail 12:172–180

    Article  PubMed  Google Scholar 

  79. Yousef M, Schannwell CM, Kostering M, Zeus T, Brehm M, Strauer BE (2009) The BALANCE Study: clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction. J Am Coll Cardiol 53:2262–2269

    Article  PubMed  Google Scholar 

  80. Zhao Q, Sun Y, Xia L, Chen A, Wang Z (2008) Randomized study of mononuclear bone marrow cell transplantation in patients with coronary surgery. Ann Thorac Surg 86:1833–1840

    Article  PubMed  Google Scholar 

  81. Akar AR, Durdu S, Arat M, Kilickap M, Kucuk NO, Arslan O et al (2009) Five-year follow-up after transepicardial implantation of autologous bone marrow mononuclear cells to ungraftable coronary territories for patients with ischaemic cardiomyopathy. Eur J Cardiothorac Surg 36:633–643

    Article  PubMed  Google Scholar 

  82. Rivas-Plata A, Castillo J, Pariona M, Chunga A (2010) Bypass grafts and cell transplant in heart failure with low ejection fraction. Asian Cardiovasc Thorac Ann 18:425–429

    Article  PubMed  Google Scholar 

  83. Turan RG, Bozdag-Turan I, Ortak J, Akin I, Kische S, Schneider H et al (2011) Improvement of cardiac function by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction. Circ J 75:683–691

    Article  PubMed  Google Scholar 

  84. Turan RG, Bozdag TI, Turan CH, Ortak J, Akin I, Kische S et al (2012) Enhanced mobilization of the bone marrow-derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction. J Cell Mol Med 16:852–864

    Article  PubMed  CAS  Google Scholar 

  85. Yao K, Huang R, Qian J, Cui J, Ge L, Li Y et al (2008) Administration of intracoronary bone marrow mononuclear cells on chronic myocardial infarction improves diastolic function. Heart 94:1147–1153

    Article  PubMed  CAS  Google Scholar 

  86. Plewka M, Krzeminska-Pakula M, Lipiec P, Peruga JZ, Jezewski T, Kidawa M et al (2009) Effect of intracoronary injection of mononuclear bone marrow stem cells on left ventricular function in patients with acute myocardial infarction. Am J Cardiol 104:1336–1342

    Article  PubMed  Google Scholar 

  87. van Ramshorst J, Antoni ML, Beeres SL, Roes SD, Delgado V, Rodrigo SF et al (2011) Intramyocardial bone marrow-derived mononuclear cell injection for chronic myocardial ischemia: the effect on diastolic function. Circ Cardiovasc Imaging 4:122–129

    Article  PubMed  Google Scholar 

  88. Olivares EL, Ribeiro VP, Werneck de Castro JP, Ribeiro KC, Mattos EC, Goldenberg RC et al (2004) Bone marrow stromal cells improve cardiac performance in healed infarcted rat hearts. Am J Physiol Heart Circ Physiol 287:H464–H470

    Article  PubMed  CAS  Google Scholar 

  89. Nagaya N, Kangawa K, Itoh T, Iwase T, Murakami S, Miyahara Y et al (2005) Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation 112:1128–1135

    Article  PubMed  Google Scholar 

  90. Kendziorra K, Barthel H, Erbs S, Emmrich F, Hambrecht R, Schuler G et al (2008) Effect of progenitor cells on myocardial perfusion and metabolism in patients after recanalization of a chronically occluded coronary artery. J Nucl Med 49:557–563

    Article  PubMed  Google Scholar 

  91. Zhang M, Methot D, Poppa V, Fujio Y, Walsh K, Murry CE (2001) Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. J Mol Cell Cardiol 33:907–921

    Article  PubMed  CAS  Google Scholar 

  92. Suzuki K, Murtuza B, Beauchamp JR, Smolenski RT, Varela-Carver A, Fukushima S et al (2004) Dynamics and mediators of acute graft attrition after myoblast transplantation to the heart. FASEB J 18:1153–1155

    PubMed  CAS  Google Scholar 

  93. Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A et al (2003) Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 108:863–868

    Article  PubMed  Google Scholar 

  94. Dow J, Simkhovich BZ, Kedes L, Kloner RA (2005) Washout of transplanted cells from the heart: a potential new hurdle for cell transplantation therapy. Cardiovasc Res 67:301–307

    Article  PubMed  CAS  Google Scholar 

  95. Hofmann M, Wollert KC, Meyer GP, Menke A, Arseniev L, Hertenstein B et al (2005) Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 111(17):2198–2202

    Article  PubMed  Google Scholar 

  96. Meluzin J, Janousek S, Mayer J, Groch L, Hornacek I, Hlinomaz O et al (2008) Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction. Int J Cardiol 128:185–192

    Article  PubMed  Google Scholar 

  97. Grajek S, Popiel M, Gil L, Breborowicz P, Lesiak M, Czepczynski R et al (2010) Influence of bone marrow stem cells on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: randomized clinical trial: impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation. Eur Heart J 31:691–702

    Article  PubMed  Google Scholar 

  98. Kawamoto A, Iwasaki H, Kusano K, Murayama T, Oyamada A, Silver M et al (2006) CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells. Circulation 114:2163–2169

    Article  PubMed  Google Scholar 

  99. Dawn B, Tiwari S, Kucia MJ, Zuba-Surma EK, Guo Y, Sanganalmath SK et al (2008) Transplantation of bone marrow-derived very small embryonic-like stem cells attenuates left ventricular dysfunction and remodeling after myocardial infarction. Stem Cells 26:1646–1655

    Article  PubMed  Google Scholar 

  100. Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W et al (2006) Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 367:113–121

    Article  PubMed  Google Scholar 

  101. Roncalli J, Mouquet F, Piot C, Trochu JN, Le Corvoisier P, Neuder Y et al (2011) Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial. Eur Heart J 32:1748–1757

    Article  PubMed  Google Scholar 

  102. Donndorf P, Kundt G, Kaminski A, Yerebakan C, Liebold A, Steinhoff G et al (2011) Intramyocardial bone marrow stem cell transplantation during coronary artery bypass surgery: a meta-analysis. J Thorac Cardiovasc Surg 142:911–920

    Article  PubMed  Google Scholar 

  103. Kucia M, Dawn B, Hunt G, Guo Y, Wysoczynski M, Majka M et al (2004) Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood following myocardial infarction. Circ Res 95:1191–1199

    Article  PubMed  CAS  Google Scholar 

  104. Kukielka GL, Hawkins HK, Michael L, Manning AM, Youker K, Lane C et al (1993) Regulation of intercellular adhesion molecule-1 (ICAM-1) in ischemic and reperfused canine myocardium. J Clin Invest 92:1504–1516

    Article  PubMed  CAS  Google Scholar 

  105. Zhang S, Sun A, Xu D, Yao K, Huang Z, Jin H et al (2009) Impact of timing on efficacy and safety of intracoronary autologous bone marrow stem cells transplantation in acute myocardial infarction: a pooled subgroup analysis of randomized controlled trials. Clin Cardiol 32:458–466

    Article  PubMed  Google Scholar 

  106. Seeger FH, Rasper T, Fischer A, Muhly-Reinholz M, Hergenreider E, Leistner DM et al (2012) Heparin disrupts the CXCR4/SDF-1 axis and impairs the functional capacity of bone marrow-derived mononuclear cells used for cardiovascular repair. Circ Res 111:854–862

    Article  PubMed  CAS  Google Scholar 

  107. Ang KL, Chin D, Leyva F, Foley P, Kubal C, Chalil S et al (2008) Randomized, controlled trial of intramuscular or intracoronary injection of autologous bone marrow cells into scarred myocardium during CABG versus CABG alone. Nat Clin Pract Cardiovasc Med 5:663–670

    Article  PubMed  Google Scholar 

  108. Hirsch A, Nijveldt R, van der Vleuten PA, Tijssen JG, van der Giessen WJ, Tio RA et al (2011) Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: results of the randomized controlled HEBE trial. Eur Heart J 32:1736–1747

    Article  PubMed  Google Scholar 

  109. Huang RC, Yao K, Zou YZ, Ge L, Qian JY, Yang J et al (2006) Long term follow-up on emergent intracoronary autologous bone marrow mononuclear cell transplantation for acute inferior-wall myocardial infarction. Zhonghua Yi Xue Za Zhi 86:1107–1110

    PubMed  Google Scholar 

  110. Beitnes JO, Hopp E, Lunde K, Smith HJ, Solheim S, Arnesen H et al (2008) Long-term follow-up of left ventricular function after acute myocardial infarction treated with intracoronary injection of autologous bone marrow cells. The ASTAMI study. Circulation 118:S_863

    Google Scholar 

  111. Beitnes JO, Hopp E, Lunde K, Solheim S, Arnesen H, Brinchmann JE et al (2009) Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the ASTAMI randomised, controlled study. Heart 95:1983–1989

    Article  PubMed  CAS  Google Scholar 

  112. Lunde K, Solheim S, Forfang K, Arnesen H, Brinch L, Bjornerheim R et al (2008) Anterior myocardial infarction with acute percutaneous coronary intervention and intracoronary injection of autologous mononuclear bone marrow cells: safety, clinical outcome, and serial changes in left ventricular function during 12-months’ follow-up. J Am Coll Cardiol 51:674–676

    Article  PubMed  Google Scholar 

  113. Meyer GP, Wollert KC, Lotz J, Pirr J, Rager U, Lippolt P et al (2009) Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial. Eur Heart J 30:2978–2984

    Article  PubMed  Google Scholar 

  114. Nogueira FB, Silva SA, Haddad AF, Peixoto CM, Carvalho RM, Tuche FA et al (2009) Systolic function of patients with myocardial infarction undergoing autologous bone marrow transplantation. Arq Bras Cardiol 93:374–379, 367–372

    Article  PubMed  Google Scholar 

  115. Quyyumi AA, Waller EK, Murrow J, Esteves F, Galt J, Oshinski J et al (2011) CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent. Am Heart J 161:98–105

    Article  PubMed  Google Scholar 

  116. Erbs S, Linke A, Schachinger V, Assmus B, Thiele H, Diederich KW et al (2007) Restoration of microvascular function in the infarct-related artery by intracoronary transplantation of bone marrow progenitor cells in patients with acute myocardial infarction: the Doppler Substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial. Circulation 116:366–374

    Article  PubMed  Google Scholar 

  117. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H et al (2006) Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J 27:2775–2783

    Article  PubMed  Google Scholar 

  118. Silva SA, Sousa AL, Haddad AF, Azevedo JC, Soares VE, Peixoto CM et al (2009) Autologous bone-marrow mononuclear cell transplantation after acute myocardial infarction: comparison of two delivery techniques. Cell Transplant 18:343–352

    Article  PubMed  Google Scholar 

  119. Srimahachota S, Boonyaratavej S, Rerkpattanapipat P, Wangsupachart S, Tumkosit M, Bunworasate U et al (2011) Intra-coronary bone marrow mononuclear cell transplantation in patients with ST-elevation myocardial infarction: a randomized controlled study. J Med Assoc Thai 94:657–663

    PubMed  Google Scholar 

  120. Suarez de Lezo J, Herrera C, Pan M, Romero M, Pavlovic D, Segura J et al (2007) Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function. Rev Esp Cardiol 60:357–365

    Article  PubMed  Google Scholar 

  121. Traverse JH, Henry TD, Ellis SG, Pepine CJ, Willerson JT, Zhao DX et al (2011) 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 306:2110–2119

    Article  PubMed  CAS  Google Scholar 

  122. Yao K, Huang R, Sun A, Qian J, Liu X, Ge L et al (2009) Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction. Eur J Heart Fail 11:691–698

    Article  PubMed  Google Scholar 

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Acknowledgments

This publication was supported in part by NIH grant R01 HL-89939. We gratefully acknowledge the expert secretarial assistance of Ms. Renee Falsken.

Conflict of Interest: None

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Medical Center, Kansas City, KS, USA

    Vinodh Jeevanantham & Mohammad R. Afzal

  2. Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland

    Ewa K. Zuba-Surma

  3. Division of Cardiovascular Diseases, University of Kansas Medical Center, Cardiovascular Research Institute, Kansas City, KS, USA

    Buddhadeb Dawn

Authors
  1. Vinodh Jeevanantham
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  2. Mohammad R. Afzal
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  3. Ewa K. Zuba-Surma
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  4. Buddhadeb Dawn
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Editor information

Editors and Affiliations

  1. , Department of Surgery, East Tennessee State University, Johnson City, 37614, Tennessee, USA

    Race L. Kao

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Jeevanantham, V., Afzal, M.R., Zuba-Surma, E.K., Dawn, B. (2013). Clinical Trials of Cardiac Repair with Adult Bone Marrow- Derived Cells. In: Kao, R. (eds) Cellular Cardiomyoplasty. Methods in Molecular Biology, vol 1036. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-511-8_15

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  • DOI: https://doi.org/10.1007/978-1-62703-511-8_15

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  • Publisher Name: Humana Press, Totowa, NJ

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