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Stamm- und progenitorzellbasierte Therapieansätze

Aktuelle Entwicklungen zur Behandlung des akuten Myokardinfarkts und der chronischen ischämischen Kardiomyopathie

Stem and progenitor cell-based therapy approaches

Current developments on treatment of acute myocardial infarction and chronic ischemic cardiomyopathy

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Zusammenfassung

Die perkutane koronare Revaskularisation sowie eine optimierte medikamentöse Therapie können bei Patienten mit akutem Myokardinfarkt das linksventrikuläre (LV) Remodeling und die LV-Dysfunktion reduzieren. Trotz dieser modernen Therapiestrategien entwickelt ein nicht unerheblicher Teil dieser Patienten ein ungünstiges kardiales Remodeling, das mit einer schlechten Prognose einhergeht. Stamm- und progenitorzellbasierte Ansätze für die Behandlung des akuten Myokardinfarkts und der chronischen ischämischen Kardiomyopathie werden als potenzielle neue therapeutische Optionen intensiv untersucht. Diese Übersicht fasst die aktuellen Entwicklungen in der stamm- und progenitorzellbasierten Therapie bei ischämischer Herzerkrankung zusammen. Dabei erfolgt eine Einschätzung der Reparatur- und Regenerationsfähigkeit verschiedener Stamm- und Progenitorzellpopulationen. Darüber hinaus werden die Vor- und Nachteile der verschiedenen kardialen Applikationsformen der Zellen und mögliche neue Strategien zur Funktionsverbesserung von Stamm- und Progenitorzellen für den Einsatz der zellbasierten kardiovaskulären Therapie dargestellt.

Abstract

Percutaneous coronary intervention (PCI) for coronary revascularization in conjunction with an optimized pharmacological treatment can reduce adverse left ventricular remodeling and dysfunction in patients with acute myocardial infarction. Despite these modern therapeutic strategies a significant number of these patients continue to develop adverse cardiac remodeling and LV dysfunction which is associated with a poor prognosis. Stem and progenitor cell-based approaches for treatment of acute myocardial infarction and chronic ischemic cardiomyopathy are an interesting direction of current experimental and clinical research. The current review article provides a summary of recent developments of cell-based therapies of ischemic heart disease, including the assessment of the repair and regeneration capacity of different stem and progenitor cell populations. In addition the advantages and disadvantages of different modes of cell application and potential strategies for the improvement of stem and progenitor cell function for their use in cell-based cardiovascular therapies will be described.

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Literatur

  1. Landmesser U, Drexler H (2005) Chronic heart failure: an overview of conventional treatment versus novel approaches. Nat Clin Pract Cardiovasc Med 2(12):628–638

    CAS  PubMed  Google Scholar 

  2. Ford ES, Ajani UA, Croft JB et al (2007) Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N Engl J Med 356(23):2388–2398

    CAS  PubMed  Google Scholar 

  3. Segers VF, Lee RT (2008) Stem-cell therapy for cardiac disease. Nature 451(7181):937–942

    CAS  PubMed  Google Scholar 

  4. Landmesser U, Wollert KC, Drexler H (2009) Potential novel pharmacological therapies for myocardial remodelling. Cardiovasc Res 81(3):519–527

    CAS  PubMed  Google Scholar 

  5. Landmesser U (2009) Bone marrow cell therapy after myocardial infarction. What should we select? Eur Heart J 30(11):1310–1312

    PubMed  Google Scholar 

  6. Schachinger V, Erbs S, Elsasser A et al (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355(12):1210–1221

    CAS  PubMed  Google Scholar 

  7. Laake LW van, Passier R, Doevendans PA, Mummery CL (2008) Human embryonic stem cell-derived cardiomyocytes and cardiac repair in rodents. Circ Res 102(9):1008–1010

    PubMed  Google Scholar 

  8. Nelson TJ, Martinez-Fernandez A, Yamada S et al (2009) Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation 120(5):408–416

    PubMed  Google Scholar 

  9. Rao MS (2004) Stem sense: a proposal for the classification of stem cells. Stem Cells Dev 13(5):452–455

    PubMed  Google Scholar 

  10. Brignier AC, Gewirtz AM (2010) Embryonic and adult stem cell therapy. J Allergy Clin Immunol 125(2 Suppl 2):S336–344

    PubMed  Google Scholar 

  11. Morrison SJ, Shah NM, Anderson DJ (1997) Regulatory mechanisms in stem cell biology. Cell 88(3):287–298

    CAS  PubMed  Google Scholar 

  12. Menasche P (2008) Skeletal myoblasts and cardiac repair. J Mol Cell Cardiol 45(4):545–553

    CAS  PubMed  Google Scholar 

  13. Menasche P, Hagege AA, Vilquin JT et al (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 41(7):1078–1083

    PubMed  Google Scholar 

  14. Assmus B, Schachinger V, Teupe C et al (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 106(24):3009–3017

    PubMed  Google Scholar 

  15. Hirsch A, Nijveldt R, Vleuten PA van der et al (2006) Intracoronary infusion of autologous mononuclear bone marrow cells or peripheral mononuclear blood cells after primary percutaneous coronary intervention: rationale and design of the HEBE trial – a prospective, multicenter, randomized trial. Am Heart J 152(3):434–441

    PubMed  Google Scholar 

  16. 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 10–16;364(9429):141–148

    Google Scholar 

  17. Templin C, Kotlarz D, Faulhaber J et al (2008) Ex vivo expanded hematopoietic progenitor cells improve cardiac function after myocardial infarction: role of beta-catenin transduction and cell dose. J Mol Cell Cardiol 45(3):394–403

    CAS  PubMed  Google Scholar 

  18. Murry CE, Soonpaa MH, Reinecke H et al (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428(6983):664–668

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  20. 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(16):2134–2139

    PubMed  Google Scholar 

  21. Giannotti G, Doerries C, Mocharla P et al (2010) Impaired in vivo endothelial repair capacity of early endothelial progenitor cells in prehypertension – relation to endothelial dysfunction. Hypertension 55:1389–1397

    CAS  PubMed  Google Scholar 

  22. Sorrentino SA, Bahlmann FH, Besler C et al (2007) Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation 116(2):163–173

    CAS  PubMed  Google Scholar 

  23. Beltrami AP, Barlucchi L, Torella D et al (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114(6):763–776

    CAS  PubMed  Google Scholar 

  24. Laugwitz KL, Moretti A, Lam J et al (2005) Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433(7026):647–653

    CAS  PubMed  Google Scholar 

  25. Oh H, Bradfute SB, Gallardo TD et al (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci USA 100(21):12313–12318

    CAS  PubMed  Google Scholar 

  26. 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(9):1015–1024

    CAS  PubMed  Google Scholar 

  27. Guan K, Wagner S, Unsold B et al (2007) Generation of functional cardiomyocytes from adult mouse spermatogonial stem cells. Circ Res 100(11):1615–1625

    CAS  PubMed  Google Scholar 

  28. Abkowitz JL, Catlin SN, McCallie MT, Guttorp P (2002) Evidence that the number of hematopoietic stem cells per animal is conserved in mammals. Blood 100(7):2665–2667

    CAS  PubMed  Google Scholar 

  29. Pittenger MF, Martin BJ (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 95(1):9–20

    CAS  PubMed  Google Scholar 

  30. Kawamoto A, Iwasaki H, Kusano K et al (2006) CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells. Circulation 114(20):2163–2169

    PubMed  Google Scholar 

  31. Losordo DW, Schatz RA, White CJ et al (2007) Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 115(25):3165–3172

    PubMed  Google Scholar 

  32. Stamm C, Kleine HD, Choi YH 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(3):717–725

    PubMed  Google Scholar 

  33. Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95(4):343–353

    CAS  PubMed  Google Scholar 

  34. Hur J, Yoon CH, Kim HS et al (2004) Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol 24(2):288–293

    CAS  PubMed  Google Scholar 

  35. Sieveking DP, Buckle A, Celermajer DS, Ng MK (2008) Strikingly different angiogenic properties of endothelial progenitor cell subpopulations: insights from a novel human angiogenesis assay. J Am Coll Cardiol 51(6):660–668

    CAS  PubMed  Google Scholar 

  36. Gruh I, Beilner J, Blomer U et al (2006) No evidence of transdifferentiation of human endothelial progenitor cells into cardiomyocytes after coculture with neonatal rat cardiomyocytes. Circulation 113(10):1326–1334

    CAS  PubMed  Google Scholar 

  37. Landmesser U, Engberding N, Bahlmann FH et al (2004) Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation 110(14):1933–1939

    CAS  PubMed  Google Scholar 

  38. (Tomita S, Li RK, Weisel RD et al (1999) Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100 (Suppl):II247–256

    Google Scholar 

  39. Conget PA, Minguell JJ (1999) Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 181(1):67–73

    CAS  PubMed  Google Scholar 

  40. Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317

    CAS  PubMed  Google Scholar 

  41. Makino S, Fukuda K, Miyoshi S et al (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103(5):697–705

    CAS  PubMed  Google Scholar 

  42. Schuleri KH, Amado LC, Boyle AJ et al (2008) Early improvement in cardiac tissue perfusion due to mesenchymal stem cells. Am J Physiol Heart Circ Physiol 294(5):H2002–2011

    CAS  PubMed  Google Scholar 

  43. Toma C, Pittenger MF, Cahill KS et al (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105(1):93–98

    PubMed  Google Scholar 

  44. Planat-Benard V, Menard C, Andre M et al (2004) Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circ Res 94(2):223–229

    CAS  PubMed  Google Scholar 

  45. Planat-Benard V, Silvestre JS, Cousin B et al (2004) Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation 109(5):656–663

    PubMed  Google Scholar 

  46. Challen GA, Little MH (2006) A side order of stem cells: the SP phenotype. Stem Cells 24(1):3–12

    PubMed  Google Scholar 

  47. Kim BO, Tian H, Prasongsukarn K et al (2005) Cell transplantation improves ventricular function after a myocardial infarction: a preclinical study of human unrestricted somatic stem cells in a porcine model. Circulation. 112 (Suppl):I96–104

    Google Scholar 

  48. Iwasaki H, Kawamoto A, Willwerth C et al (2009) Therapeutic potential of unrestricted somatic stem cells isolated from placental cord blood for cardiac repair post myocardial infarction. Arterioscler Thromb Vasc Biol 29(11):1830–1835

    CAS  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(9):1189–1200

    PubMed  Google Scholar 

  50. Dib N, Dinsmore J, Lababidi Z et al (2009) One-year follow-up of feasibility and safety of the first U.S., randomized, controlled study using 3-dimensional guided catheter-based delivery of autologous skeletal myoblasts for ischemic cardiomyopathy (CAuSMIC study). JACC Cardiovasc Interv 2(1):9–16

    PubMed  Google Scholar 

  51. Hierlihy AM, Seale P, Lobe CG et al (2002) The post-natal heart contains a myocardial stem cell population. FEBS Lett 530(1–3):239–243

    Google Scholar 

  52. Smith RR, Barile L, Messina E, Marban E (2008) Stem cells in the heart: what’s the buzz all about? – Part 1: preclinical considerations. Heart Rhythm 5(5):749–757

    PubMed  Google Scholar 

  53. Messina E, De Angelis L, Frati G et al (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95(9):911–921

    CAS  PubMed  Google Scholar 

  54. Li Z, Lee A, Huang M et al (2009) Imaging survival and function of transplanted cardiac resident stem cells. J Am Coll Cardiol 53(14):1229–1240

    CAS  PubMed  Google Scholar 

  55. Guan K, Nayernia K, Maier LS et al (2006) Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 440(7088):1199–1203

    CAS  PubMed  Google Scholar 

  56. Smith AG (2001) Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol 17:435–462

    CAS  PubMed  Google Scholar 

  57. Crisostomo PR, Abarbanell AM, Wang M et al (2008) Embryonic stem cells attenuate myocardial dysfunction and inflammation after surgical global ischemia via paracrine actions. Am J Physiol Heart Circ Physiol 295(4):H1726–1735

    CAS  PubMed  Google Scholar 

  58. Min JY, Yang Y, Sullivan MF et al (2003) Long-term improvement of cardiac function in rats after infarction by transplantation of embryonic stem cells. J Thorac Cardiovasc Surg 125(2):361–369

    PubMed  Google Scholar 

  59. Nussbaum J, Minami E, Laflamme MA et al (2007) Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response. FASEB J 21(7):1345–1357

    CAS  PubMed  Google Scholar 

  60. Caspi O, Huber I, Kehat I et al (2007) Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol 50(19):1884–1893

    PubMed  Google Scholar 

  61. Passier R, Laake LW van, Mummery CL (2008) Stem-cell-based therapy and lessons from the heart. Nature 453(7193):322–329

    CAS  PubMed  Google Scholar 

  62. Murry CE, Keller G (2008) Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell 132(4):661–680

    CAS  PubMed  Google Scholar 

  63. Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872

    CAS  PubMed  Google Scholar 

  64. Yu J, Vodyanik MA, Smuga-Otto K et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920

    CAS  PubMed  Google Scholar 

  65. Mauritz C, Schwanke K, Reppel M et al (2008) Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation 118(5):507–517

    PubMed  Google Scholar 

  66. Okita K, Nakagawa M, Hyenjong H et al (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322(5903):949–953

    CAS  PubMed  Google Scholar 

  67. Kim D, Kim CH, Moon JI et al (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4(6):472–476

    CAS  PubMed  Google Scholar 

  68. Zhang J, Wilson GF, Soerens AG et al (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res 104(4):e30–41

    CAS  PubMed  Google Scholar 

  69. 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(7):863–868

    PubMed  Google Scholar 

  70. 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(15):1913–1918

    PubMed  Google Scholar 

  71. Sherman W, Martens TP, Viles-Gonzalez JF, Siminiak T (2006) Catheter-based delivery of cells to the heart. Nat Clin Pract Cardiovasc Med 3 (Suppl 1):S57–64

    PubMed  Google Scholar 

  72. Perin EC, Lopez J (2006) Methods of stem cell delivery in cardiac diseases. Nat Clin Pract Cardiovasc Med 3 (Suppl 1):S110–113

    PubMed  Google Scholar 

  73. 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(11):1964–1971

    PubMed  Google Scholar 

  74. Price MJ, Chou CC, Frantzen M et al (2006) Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol 111(2):231–239

    PubMed  Google Scholar 

  75. Templin C, Kotlarz D, Marquart F et al (2006) Transcoronary delivery of bone marrow cells to the infarcted murine myocardium: feasibility, cellular kinetics, and improvement in cardiac function. Basic Res Cardiol 101(4):301–310

    PubMed  Google Scholar 

  76. Tossios P, Krausgrill B, Schmidt M et al (2008) Role of balloon occlusion for mononuclear bone marrow cell deposition after intracoronary injection in pigs with reperfused myocardial infarction. Eur Heart J 29(15):1911–1921

    CAS  PubMed  Google Scholar 

  77. Vulliet PR, Greeley M, Halloran SM et al (2004) Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 363(9411):783–784

    PubMed  Google Scholar 

  78. 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(9):1114–1122

    PubMed  Google Scholar 

  79. Moscoso I, Barallobre J, Ilarduya OM de et al (2009) Analysis of different routes of administration of heterologous 5-azacytidine-treated mesenchymal stem cells in a porcine model of myocardial infarction. Transplant Proc 41(6):2273–2275

    CAS  PubMed  Google Scholar 

  80. Makela J, Anttila V, Ylitalo K et al (2009) Acute homing of bone marrow-derived mononuclear cells in intramyocardial vs. intracoronary transplantation. Scand Cardiovasc J 43(6):366–373

    PubMed  Google Scholar 

  81. Smits PC, Geuns RJ van, 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(12):2063–2069

    PubMed  Google Scholar 

  82. Fukushima S, Varela-Carver A, Coppen SR et al (2007) Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model. Circulation 115(17):2254–2261

    PubMed  Google Scholar 

  83. Melo LG, Pachori AS, Kong D et al (2004) Gene and cell-based therapies for heart disease. FASEB J 18(6):648–663

    CAS  PubMed  Google Scholar 

  84. Raake P, Degenfeld G von, Hinkel R et al (2004) Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins: comparison with surgical and percutaneous intramyocardial gene delivery. J Am Coll Cardiol 44(5):1124–1129

    CAS  PubMed  Google Scholar 

  85. 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(10):989–997

    PubMed  Google Scholar 

  86. 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(3):727–733

    CAS  PubMed  Google Scholar 

  87. Lipinski MJ, Biondi-Zoccai GG, Abbate A 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(18):1761–1767

    PubMed  Google Scholar 

  88. Martin-Rendon E, Brunskill SJ, Hyde CJ et al (2008) Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review. Eur Heart J 29(15):1807–1818

    CAS  PubMed  Google Scholar 

  89. 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 (Suppl):I178–183

    PubMed  Google Scholar 

  90. Reffelmann T, Konemann S, Kloner RA (2009) Promise of blood- and bone marrow-derived stem cell transplantation for functional cardiac repair: putting it in perspective with existing therapy. J Am Coll Cardiol 53(4):305–308

    PubMed  Google Scholar 

  91. Meyer GP, Wollert KC, Lotz J 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(24):2978–2984

    PubMed  Google Scholar 

  92. 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(9505):113–121

    PubMed  Google Scholar 

  93. Erbs S, Linke A, Schachinger V 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(4):366–374

    PubMed  Google Scholar 

  94. 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(23):2775–2783

    PubMed  Google Scholar 

  95. Assmus B, Rolf A, Erbs S et al (2010) Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail 3(1):89–96

    PubMed  Google Scholar 

  96. 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(10):1287–1294

    PubMed  Google Scholar 

  97. Lunde K, Solheim S, Forfang K 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(6):674–676

    PubMed  Google Scholar 

  98. Tendera M, Wojakowski W, Ruzyllo 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(11):1313–1321

    PubMed  Google Scholar 

  99. Seeger FH, Tonn T, Krzossok N et al (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(6):766–772

    PubMed  Google Scholar 

  100. 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(8):1690–1699

    PubMed  Google Scholar 

  101. Sanchez PL, Sanz-Ruiz R, Fernandez-Santos ME, Fernandez-Aviles F (2010) Cultured and freshly isolated adipose tissue-derived cells: fat years for cardiac stem cell therapy. Eur Heart J 31(4):394–397

    PubMed  Google Scholar 

  102. Burt RK, Loh Y, Pearce W et al (2008) Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA 299(8):925–936

    CAS  PubMed  Google Scholar 

  103. Orlic D, Kajstura J, Chimenti S et al (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410(6829):701–705

    CAS  PubMed  Google Scholar 

  104. Gnecchi M, Zhang Z, Ni A, Dzau VJ (2008) Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res 103(11):1204–1219

    CAS  PubMed  Google Scholar 

  105. 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(4):430–436

    CAS  PubMed  Google Scholar 

  106. Giordano FJ, Gerber HP, Williams SP et al (2001) A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc Natl Acad Sci U S A 98(10):5780–5785

    CAS  PubMed  Google Scholar 

  107. Uemura R, Xu M, Ahmad N, Ashraf M (2006) Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res 98(11):1414–1421

    CAS  PubMed  Google Scholar 

  108. Urbich C, Aicher A, Heeschen C et al (2005) Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol 39(5):733–742

    CAS  PubMed  Google Scholar 

  109. Burchfield JS, Iwasaki M, Koyanagi M et al (2008) Interleukin-10 from transplanted bone marrow mononuclear cells contributes to cardiac protection after myocardial infarction. Circ Res 103(2):203–211

    CAS  PubMed  Google Scholar 

  110. Gnecchi M, He H, Liang OD et al (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11(4):367–368

    CAS  PubMed  Google Scholar 

  111. Mirotsou M, Zhang Z, Deb A et al (2007) Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci USA 104(5):1643–1648

    CAS  PubMed  Google Scholar 

  112. Luecke N, Templin C, Muetzelburg MV et al (2010) Secreted proteome of the murine multipotent hematopoietic progenitor cell line DKmix. Rapid Commun Mass Spectrom 24(5):561–570

    CAS  PubMed  Google Scholar 

  113. Kinnaird T, Stabile E, Burnett MS et al (2004) Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res 94(5):678–685

    CAS  PubMed  Google Scholar 

  114. Yoon CH, Koyanagi M, Iekushi K et al (2010) Mechanism of improved cardiac function after bone marrow mononuclear cell therapy: role of cardiovascular lineage commitment. Circulation 121(18):2001–2011

    PubMed  Google Scholar 

  115. 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(12):1199–1209

    CAS  PubMed  Google Scholar 

  116. Hofmann M, Wollert KC, Meyer GP et al (2005) Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 111(17):2198–2202

    PubMed  Google Scholar 

  117. Schachinger V, Aicher A, Dobert N et al (2008) Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium. Circulation 118(14):1425–1432

    PubMed  Google Scholar 

  118. Vasa M, Fichtlscherer S, Aicher A et al (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89(1):E1–7

    CAS  PubMed  Google Scholar 

  119. Imanishi T, Moriwaki C, Hano T, Nishio I (2005) Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension. J Hypertens 23(10):1831–1837

    CAS  PubMed  Google Scholar 

  120. Pons J, Huang Y, Arakawa-Hoyt J et al (2008) VEGF improves survival of mesenchymal stem cells in infarcted hearts. Biochem Biophys Res Commun 376(2):419–422

    CAS  PubMed  Google Scholar 

  121. Pons J, Huang Y, Takagawa J et al (2009) Combining angiogenic gene and stem cell therapies for myocardial infarction. J Gene Med 11(9):743–753

    CAS  PubMed  Google Scholar 

  122. Tang J, Wang J, Yang J et al (2009) Mesenchymal stem cells over-expressing SDF-1 promote angiogenesis and improve heart function in experimental myocardial infarction in rats. Eur J Cardiothorac Surg 36(4):644–650

    PubMed  Google Scholar 

  123. Zhao T, Zhang D, Millard RW et al (2009) Stem cell homing and angiomyogenesis in transplanted hearts are enhanced by combined intramyocardial SDF-1alpha delivery and endogenous cytokine signaling. Am J Physiol Heart Circ Physiol 296(4):H976–986

    CAS  PubMed  Google Scholar 

  124. Templin C, Kotlarz D, Rathinam C et al (2008) Establishment of immortalized multipotent hematopoietic progenitor cell lines by retroviral-mediated gene transfer of beta-catenin. Exp Hematol 36(2):204–215

    CAS  PubMed  Google Scholar 

  125. Yang J, Zhou W, Zheng W et al (2007) Effects of myocardial transplantation of marrow mesenchymal stem cells transfected with vascular endothelial growth factor for the improvement of heart function and angiogenesis after myocardial infarction. Cardiology 107(1):17–29

    PubMed  Google Scholar 

  126. Cheng Z, Ou L, Zhou X et al (2008) Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther 16(3):571–579

    CAS  PubMed  Google Scholar 

  127. Tang YL, Tang Y, Zhang YC et al (2005) Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J Am Coll Cardiol 46(7):1339–1350

    CAS  PubMed  Google Scholar 

  128. Zaruba MM, Theiss HD, Vallaster M et al (2009) Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction. Cell Stem Cell 4(4):313–323

    CAS  PubMed  Google Scholar 

  129. Spyridopoulos I, Haendeler J, Urbich C et al (2004) Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor TRF2 in endothelial progenitor cells. Circulation 110(19):3136–3142

    CAS  PubMed  Google Scholar 

  130. Shao H, Tan Y, Eton D et al (2008) Statin and stromal cell-derived factor-1 additively promote angiogenesis by enhancement of progenitor cells incorporation into new vessels. Stem Cells 26(5):1376–1384

    CAS  PubMed  Google Scholar 

  131. Rooij E van, Marshall WS, Olson EN (2008) Toward microRNA-based therapeutics for heart disease: the sense in antisense. Circ Res 103(9):919–928

    PubMed  Google Scholar 

  132. Suarez Y, FernandezHernando C, Pober JS, Sessa WC (2007) Dicer-dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res 100(8):1164–1173

    CAS  PubMed  Google Scholar 

  133. Suarez Y, Sessa WC (2009) MicroRNAs as novel regulators of angiogenesis. Circ Res 104(4):442–454

    CAS  PubMed  Google Scholar 

  134. Maisch B (2010) Regeneration in der Kardiologie – Innovation oder Illusion?. Herz 35:307–308

    Google Scholar 

  135. Bergmann MW, Jaquet K, Schneider C et al (2010) Aktuelle Datenlage zur interventionellen, intramyokardialen Stammzelltherapie bei ischämischer Kardiomyopathie. Herz 35:317–323

    CAS  PubMed  Google Scholar 

  136. Cebotari S, Tudorache I, Schilling T, Haverich A (2010) Tissue Engineering von Herzklappen und Myokard. Herz 35:334–341

    PubMed  Google Scholar 

  137. Kaminski A, Donndorf P, Klopsch C, Steinhoff G (2010) Chirurgische intramyokardiale Stammzelltherapie bei chronischer Myokardischämie. Herz 35:324–333

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Klinik für Kardiologie, UniversitätsSpital Zürich, Rämistr. 100, 8091, Zürich, Schweiz

    C. Templin MD, T.F. Lüscher & U. Landmesser MD

  2. Kardiovaskuläre Forschung, Institut für Physiologie, Universität Zürich, Zürich, Schweiz

    T.F. Lüscher

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  1. C. Templin MD
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  2. T.F. Lüscher
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  3. U. Landmesser MD
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Correspondence to C. Templin MD or U. Landmesser MD.

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Das Verfassen des Artikels wurde teilweise unterstützt durch ein Forschungsprogramm des Schweizerischen Nationalfonds „Sonderprogramm Universitäre Medizin“ [Nr. 33CM30–124112/1].

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Templin, C., Lüscher, T. & Landmesser, U. Stamm- und progenitorzellbasierte Therapieansätze. Herz 35, 445–457 (2010). https://doi.org/10.1007/s00059-010-3397-0

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