Der Internist

, Volume 47, Issue 11, pp 1177–1182

Regenerative Therapien in der Kardiologie

Wie weit entfernt von der Praxis?
Arzneimitteltherapie
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Zusammenfassung

Beim akuten Myokardinfarkt geht kontraktiles Myokardgewebe verloren. Durch Umbauprozesse kommt es zum Remodeling des linken Ventrikels, welches in Herzinsuffizienz mündet. Neben einer optimierten akuten Reperfusionstherapie und einer medikamentösen Postinfarkttherapie kann durch die Verbesserung der Durchblutung mittels Gefäßneubildung sowie Regeneration von Kardiomyozyten im Bereich des Infarktes das Remodeling vermindert oder aufgehoben werden. Experimentelle Studien zeigen, dass durch die Transplantation von adulten Stammzellen die Neovaskularisierung verbessert und die Fibrosierung reduziert werden kann und somit die linksventrikuläre Funktion nach einem akuten Myokardinfarkt gesteigert wird. Im Gegensatz zur bisherigen Therapiestrategie bietet die Stamm- oder Progenitorzelltherapie eine Möglichkeit, Myokardgewebe zu regenerieren. Erste klinische Untersuchungen belegen neben Sicherheit und Machbarkeit einer Therapie mit autologen Progenitorzellen eine ausgeprägte Besserung der linksventrikulären Funktion, Geometrie und Vaskularisierung bei Patienten mit akutem Myokardinfarkt, die mit einer intrakoronaren Zelltherapie behandelt wurden. Bei Patienten mit chronisch-ischämischer Kardiomyopathie ist die Verbesserung der Kontraktilität derzeit noch geringer ausgeprägt. Ob durch eine intrakoronare Infusion von autologen adulten Progenitorzellen auch eine Reduktion von Morbidität und Mortalität bei Herzinsuffizienz erreicht werden kann, wird in derzeit in Planung befindlichen Studien untersucht werden.

Schlüsselwörter

Progenitorzellen Myokardinfarkt Neovaskularisierung Ischämische Kardiomyopathie Remodeling 

Regenerative therapy in cardiology

How distant is it from reality?

Abstract

During acute myocardial infarction, ischemia causes progressive loss of contractile tissue. Subsequently, structural changes lead to left ventricular remodeling finally resulting in the development of heart failure. In addition to an optimal reperfusion and pharmacologinal post-infarction therapy, increased neovascularization and regeneration of cardiomyocytes could reduce or even abolish the ongoing left ventricular remodeling processes within the infarct area. Experimental studies have demonstrated that transplantation of adult progenitor cells leads to increased neovascularization, reduced fibrosis and, therefore, increased left ventricular function after acute myocardial infarction. In contrast to current treatment strategies, progenitor cell therapy offers a new regenerative approach for myocardial tissue. Initial clinical studies have demonstrated, apart from safety and feasibility of intracoronary infusion of adult autologous progenitor cells, a significant improvement of left ventricular function, geometry and vascularization in patients with acute myocardial infarction receiving intracoronary infusion of progenitor cells. However, in patients with chronic ischemic cardiomyopathy, the improvement in contractility is less pronounced. Finally, whether intracoronary infusion of adult progenitor cells can also reduce morbidity and mortality due to heart failure, remains to be investigated.

Keywords

Progenitor cells Myocardial infarction Neovascularization Ischemic cardiomyopathy Remodeling 

Literatur

  1. 1.
    (2000) 2001 Heart and stroke statistical update. Dallas: American Heart AssociationGoogle Scholar
  2. 2.
    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: 2134–2139CrossRefPubMedGoogle Scholar
  3. 3.
    Assmus B, Honold J, Schächinger V et al. (2006) Transcoronary transplantation of progenitor cells for left ventricular dysfunction after myocardial infarction. N Engl J Med (in press)Google Scholar
  4. 4.
    Assmus B, Schachinger V, Teupe C et al. (2002) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 106: 3009–3017CrossRefPubMedGoogle Scholar
  5. 5.
    Britten MB, Abolmaali ND, Assmus B 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: 2212–2218CrossRefPubMedGoogle Scholar
  6. 6.
    Dimmeler S, Zeiher AM, Schneider MD (2005) Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 115: 572–583CrossRefPubMedGoogle Scholar
  7. 7.
    Zohlnhöfer D, Ott I, Mehilli J et al., for the REVIVAL-2 Investigators (2006) Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: A randomized controlled trial. JAMA 295:1003–1010 CrossRefPubMedGoogle Scholar
  8. 8.
    Ince H, Petzsch M, Kleine HD et al. (2005) Prevention of left ventricular remodeling with granulocyte colony-stimulating factor after acute myocardial infarction: final 1-year results of the Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor (FIRSTLINE-AMI) Trial. Circulation 112: 173–180CrossRefGoogle Scholar
  9. 9.
    Jackson KA, Majka SM, Wang H et al. (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107: 1395–1402PubMedGoogle Scholar
  10. 10.
    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: 113–121CrossRefPubMedGoogle Scholar
  11. 11.
    Kawamoto A, Gwon HC, Iwaguro H et al. (2001) Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 103: 634–637PubMedGoogle Scholar
  12. 12.
    Lunde K, Solheim S, Aakhus S et al. (2005) Effects on left ventricular function by intracoronary injections of autologous mononuclear bone marrow cells in acute anterior wall myocardial infarction: the ASTAMI Randomized Controlled Trial. Circulation 112: 3364Google Scholar
  13. 13.
    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: 1287–1294CrossRefPubMedGoogle Scholar
  14. 14.
    Orlic D, Kajstura J, Chimenti S et al. (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410: 701–705CrossRefPubMedGoogle Scholar
  15. 15.
    Orlic D, Kajstura J, Chimenti S et al. (2001) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 98: 10344–10349CrossRefPubMedGoogle Scholar
  16. 16.
    Perin EC, Dohmann HF, Borojevic R et al. (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107: 2294–2302CrossRefPubMedGoogle Scholar
  17. 17.
    Pfeffer MA, McMurray JJ, Velazquez EJ et al. (2003) Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 349: 1893–1906CrossRefPubMedGoogle Scholar
  18. 18.
    Pitt B, Remme W, Zannad F et al. (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348: 1309–1321CrossRefPubMedGoogle Scholar
  19. 19.
    Quaini F, Urbanek K, Beltrami AP et al. (2002) Chimerism of the transplanted heart. N Engl J Med 346: 5–15CrossRefPubMedGoogle Scholar
  20. 20.
    Schmidt-Lucke C, Rössig L, Fichtlscherer S et al. (2005) Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events proof of concept for the clinical importance of endogenous vascular repair. Circulation 111: 2981–2987CrossRefPubMedGoogle Scholar
  21. 21.
    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: 1690–1699CrossRefPubMedGoogle Scholar
  22. 22.
    Schächinger V, Assmus B, Honold J et al. (2006) Normalization of coronary blood flow in the infarct-related artery after intracoronary progenitor cell therapy: intracoronary Doppler substudy of the TOPCARE-AMI trial. Clin Res Cardiol (in press)Google Scholar
  23. 23.
    Schachinger V, Tonn T, Dimmeler S, Zeiher AM (2006) Bone-marrow-derived progenitor cell therapy in need of proof of concept: design of the REPAIR-AMI trial. Nat Clin Pract Cardiovasc Med 3 [Suppl 1]:S23–28Google Scholar
  24. 24.
    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: 1913–1918CrossRefPubMedGoogle Scholar
  25. 25.
    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: 141–148CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2006

Authors and Affiliations

  1. 1.Medizinische Klinik III, KardiologieJohann-Wolfgang-Goethe-Universität FrankfurtFrankfurtDeutschland

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