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Methods of Cell Delivery for Cardiac Repair

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Regenerating the Heart

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Cellular cardiomyoplasty describes the procedure of cell delivery to the injured heart with the goal to either reverse or at least halt the detrimental effects of myocardial injury. Several strategies for cell delivery to the injured myocardium are available. Direct intramyocardial injection may be performed using a transepicardial, surgical, transendocardial, or transvenous approach. Other strategies include the delivery of cells through coronary arteries, coronary veins, or peripheral veins. In this chapter, we review the successes and the shortcomings of the various procedures that have been tried in animal models of cardiac injury and clinically in patient trials.

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References

  1. Baklanov DV, Moodie KM, McCarthy FE, et al (2006) Comparison of transendocardial and retrograde coronary venous intramyocardial catheter delivery systems in healthy and infarcted pigs. Catheter Cardiovasc Interv 68:416–423

    Article  PubMed  CAS  Google Scholar 

  2. Freyman T, Polin G, Osman H, et al (2006) A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J 27:1114–1122

    Article  PubMed  Google Scholar 

  3. Fukushima S, Coppen SR, Lee J, et al (2008) Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat. PLoS One 3:e3071

    Article  PubMed  Google Scholar 

  4. George JC, Goldberg J, Joseph M, et al (2008) Transvenous intramyocardial cellular delivery increases retention in comparison to intracoronary delivery in a porcine model of acute myocardial infarction. J Interv Cardiol 21:424–431

    Article  PubMed  Google Scholar 

  5. Grogaard HK, Sigurjonsson OE, Brekke M, et al (2007) Cardiac accumulation of bone marrow mononuclear progenitor cells after intracoronary or intravenous injection in pigs subjected to acute myocardial infarction with subsequent reperfusion. Cardiovasc Revasc Med 8:21–27

    Article  PubMed  Google Scholar 

  6. Hale SL, Dai W, Dow JS, et al (2008) Mesenchymal stem cell administration at coronary artery reperfusion in the rat by two delivery routes: a quantitative assessment. Life Sci 83:511–515

    Article  PubMed  CAS  Google Scholar 

  7. Hamdi H, Furuta A, Bellamy V, et al (2009) Cell delivery: intramyocardial injections or epicardial deposition? A head-to-head comparison. Ann Thorac Surg 87:1196–1203

    Article  PubMed  Google Scholar 

  8. Hayashi M, Li TS, Ito H, et al (2004) Comparison of intramyocardial and intravenous routes of delivering bone marrow cells for the treatment of ischemic heart disease: an experimental study. Cell Transplant 13:639–647

    Article  PubMed  Google Scholar 

  9. Hou D, Youssef EA, Brinton TJ, et al (2005) Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 112:I150–I156

    PubMed  Google Scholar 

  10. Li SH, Lai TY, Sun Z, et al (2009) Tracking cardiac engraftment and distribution of implanted bone marrow cells: comparing intra-aortic, intravenous, and intramyocardial delivery. J Thorac Cardiovasc Surg 137:1225.e1–1233.e1

    Google Scholar 

  11. Sun Z, Wu J, Fujii H, et al (2008) Human angiogenic cell precursors restore function in the infarcted rat heart: a comparison of cell delivery routes. Eur J Heart Fail 10:525–533

    Article  PubMed  CAS  Google Scholar 

  12. Anderl JN, Robey TE, Stayton PS, et al (2009) Retention and biodistribution of microspheres injected into ischemic myocardium. J Biomed Mater Res A 88:704–710

    PubMed  Google Scholar 

  13. Yasuda T, Weisel RD, Kiani C, et al (2005) Quantitative analysis of survival of transplanted smooth muscle cells with real-time polymerase chain reaction. J Thorac Cardiovasc Surg 129:904–911

    Article  PubMed  Google Scholar 

  14. Muller-Ehmsen J, Krausgrill B, Burst V, et al (2006) Effective engraftment but poor mid-term persistence of mononuclear and mesenchymal bone marrow cells in acute and chronic rat myocardial infarction. J Mol Cell Cardiol 41:876–884

    Article  PubMed  Google Scholar 

  15. Perin EC, Silva GV, Assad JA, et al (2008) Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J Mol Cell Cardiol 44:486–495

    Article  PubMed  CAS  Google Scholar 

  16. Ben-Dor I, Fuchs S, and Kornowski R (2006) Potential hazards and technical considerations associated with myocardial cell transplantation protocols for ischemic myocardial syndrome. J Am Coll Cardiol 48:1519–1526

    Article  PubMed  Google Scholar 

  17. Vulliet PR, Greeley M, Halloran SM, et al (2004) Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 363:783–784

    Article  PubMed  Google Scholar 

  18. Kang HJ, Kim HS, Zhang SY, 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 

  19. Morishima I, Sone T, Okumura K, et al (2000) Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol 36:1202–1209

    Article  PubMed  CAS  Google Scholar 

  20. Reffelmann T, Hale SL, Dow JS, et al (2003) No-reflow phenomenon persists long-term after ischemia/reperfusion in the rat and predicts infarct expansion. Circulation 108:2911–2917

    Article  PubMed  Google Scholar 

  21. Barbash IM, Chouraqui P, Baron J, 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 

  22. Abdel-Latif A, Bolli R, Tleyjeh IM, 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 

  23. Aicher A, Brenner W, Zuhayra M, et al (2003) Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 107:2134–2139

    Article  PubMed  Google Scholar 

  24. Laflamme MA, Chen KY, Naumova AV, et al (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25:1015–1024

    Article  PubMed  CAS  Google Scholar 

  25. Kocher AA, Schuster MD, Szabolcs MJ, 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  PubMed  CAS  Google Scholar 

  26. Gao J, Dennis JE, Muzic RF, et al (2001) The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 169:12–20

    Article  PubMed  CAS  Google Scholar 

  27. Strauer BE, Brehm M, Zeus T, 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 

  28. Chen SL, Fang WW, Ye F, 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 

  29. Fernandez-Aviles F, San Roman JA, Garcia-Frade J, et al (2004) Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res 95:742–748

    Article  PubMed  CAS  Google Scholar 

  30. Janssens S, Dubois C, Bogaert J, 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 

  31. Kang HJ, Lee HY, Na SH, 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 

  32. Meyer GP, Wollert KC, Lotz J, 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 

  33. Wollert KC, Meyer GP, Lotz J, 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 

  34. Zohlnhofer D, Ott I, Mehilli J, et al (2006) Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial. JAMA 295:1003–1010

    Article  PubMed  Google Scholar 

  35. Lunde K, Solheim S, Aakhus S, 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 

  36. Schachinger V, Assmus B, Britten MB, 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 

  37. Schachinger V, Erbs S, Elsasser A, 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 

  38. Schachinger V, Erbs S, Elsasser A, 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 

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

    Article  PubMed  CAS  Google Scholar 

  40. Assmus B, Honold J, Schachinger V, et al (2006) Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 355:1222–1232

    Article  PubMed  CAS  Google Scholar 

  41. Seeger FH, Zeiher AM, and Dimmeler S (2007) Cell-enhancement strategies for the treatment of ischemic heart disease. Nat Clin Pract Cardiovasc Med 4 Suppl 1:S110–S113

    Article  PubMed  CAS  Google Scholar 

  42. Menasche P, Hagege AA, Scorsin M, et al (2001) Myoblast transplantation for heart failure. Lancet 357:279–280

    Article  PubMed  CAS  Google Scholar 

  43. Stamm C, Westphal B, Kleine HD, et al (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361:45–46

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  45. Perin EC, Geng YJ, and Willerson JT (2003) Adult stem cell therapy in perspective. Circulation 107:935–938

    Article  PubMed  Google Scholar 

  46. Hagege AA, Marolleau JP, Vilquin JT, et al (2006) Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first phase I cohort of patients. Circulation 114:I108–I113

    Article  PubMed  Google Scholar 

  47. Dib N, Michler RE, Pagani FD, et al (2005) Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation 112:1748–1755

    Article  PubMed  Google Scholar 

  48. Herreros J, Prosper F, Perez A, et al (2003) Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction. Eur Heart J 24:2012–2020

    Article  PubMed  Google Scholar 

  49. Menasche P, Alfieri O, Janssens S, et al (2008) The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 117:1189–1200

    Article  PubMed  Google Scholar 

  50. Pagani FD, DerSimonian H, Zawadzka A, et al (2003) Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. J Am Coll Cardiol 41:879–888

    Article  PubMed  Google Scholar 

  51. Siminiak T, Kalawski R, Fiszer D, et al (2004) Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. Am Heart J 148:531–537

    Article  PubMed  Google Scholar 

  52. van Ramshorst J, Bax JJ, Beeres SL, et al (2009) Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA 301:1997–2004

    Article  PubMed  Google Scholar 

  53. Opie SR and Dib N (2006) Surgical and catheter delivery of autologous myoblasts in patients with congestive heart failure. Nat Clin Pract Cardiovasc Med 3 Suppl 1:S42–S45

    Article  PubMed  Google Scholar 

  54. Vale PR, Losordo DW, Milliken CE, et al (2000) Left ventricular electromechanical mapping to assess efficacy of phVEGF(165) gene transfer for therapeutic angiogenesis in chronic myocardial ischemia. Circulation 102:965–974

    PubMed  CAS  Google Scholar 

  55. Kawamoto A, Gwon HC, Iwaguro H, et al (2001) Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 103:634–637

    PubMed  CAS  Google Scholar 

  56. Smits PC, van Geuns RJ, Poldermans D, et al (2003) Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol 42:2063–2069

    Article  PubMed  Google Scholar 

  57. Thompson CA, Nasseri BA, Makower J, et al (2003) Percutaneous transvenous cellular cardiomyoplasty. A novel nonsurgical approach for myocardial cell transplantation. J Am Coll Cardiol 41:1964–1971

    Article  PubMed  Google Scholar 

  58. Perin EC, Munger T, Pandey A, et al (2007) First experience with remote LV mapping and injection utilizing a novel integrated NOGA XP/stereotaxis platform. EuroInterv 3:142–148

    Google Scholar 

  59. Grossman PM, Han Z, Palasis M, et al (2002) Incomplete retention after direct myocardial injection. Catheter Cardiovasc Interv 55:392–397

    Article  PubMed  Google Scholar 

  60. Thompson CA, Reddy VK, Srinivasan A, et al (2005) Left ventricular functional recovery with percutaneous, transvascular direct myocardial delivery of bone marrow-derived cells. J Heart Lung Transplant 24:1385–1392

    Article  PubMed  Google Scholar 

  61. Siminiak T, Fiszer D, Jerzykowska O, et al (2005) Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: the POZNAN trial. Eur Heart J 26:1188–1195

    Article  PubMed  Google Scholar 

  62. Patel AN and Sherman W (2007) Cardiac stem cell therapy from bench to bedside. Cell Transplant 16:875–878

    Article  PubMed  Google Scholar 

  63. Reyes G, Allen KB, Aguado B, et al (2009) Bone marrow laser revascularisation for treating refractory angina due to diffuse coronary heart disease. Eur J Cardiothorac Surg 36:192–194

    Article  PubMed  Google Scholar 

  64. Muller-Ehmsen J, Whittaker P, Kloner RA, et al (2002) Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium. J Mol Cell Cardiol 34:107–116

    Article  PubMed  Google Scholar 

  65. Zhang M, Methot D, Poppa V, et al (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 

  66. Christman KL, Vardanian AJ, Fang Q, et al (2004) Injectable fibrin scaffold improves cell transplant survival, reduces infarct expansion, and induces neovasculature formation in ischemic myocardium. J Am Coll Cardiol 44:654–660

    Article  PubMed  CAS  Google Scholar 

  67. Bartunek J, Vanderheyden M, Vandekerckhove B, 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 

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Authors and Affiliations

  1. Center for Cardiovascular Biology, University of Washington Medicine at South Lake Union, Seattle, WA, USA

    Hans Reinecke

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  1. Sarah Fernandes
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  2. Hans Reinecke
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Correspondence to Hans Reinecke .

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Editors and Affiliations

  1. Health Sciences Center, Dept. Physiology & Biophysics, Stony Brook University, Stony Brook, 11794-8661, New York, USA

    Ira S. Cohen

  2. Worcester Polytechnic Institute, Institute Rd. 100, Worcester, 01609-2280, Massachusetts, USA

    Glenn R. Gaudette

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Fernandes, S., Reinecke, H. (2011). Methods of Cell Delivery for Cardiac Repair. In: Cohen, I., Gaudette, G. (eds) Regenerating the Heart. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-61779-021-8_24

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