Skip to main content

Advertisement

SpringerLink
Log in

Mesenchymale Stammzellen zur kardialen Regeneration

HOT: heranzüchten, optimieren, transplantieren

Mesenchymal stem cells for cardiac regeneration

HOT: harvest, optimize, transplant

  • Stand der Wissenschaft
  • Published:
Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Die Ansiedlung von mesenchymalen Stammzellen („mesenchymal stem cells“, MSC) war als potenzieller Ansatz in der Therapie der kardialen Dysfunktion bezeichnet worden. Dennoch wird die regenerative Kapazität dieser Methode durch begrenztes Zellüberleben eingeschränkt. Nach passagerer Überexpression des antiapoptotischen Gens BCL-2 in MSC (BCL-2-MSC) unter Verwendung eines nichtviralen, polymerbasierten Gentransfersystems zeigen sich im Rattenexperiment nach Ligatur des R. interventricularis anterior (RIVA) und Injektion der BCL-2-MSC in den Infarktrandbezirk verbessertes Zellüberleben in vivo, eine signifikant kleinere Infarktgröße und höhere Kapillardichte. BCL-2-MSC weisen in vitro unter hypoxischen Bedingungen eine signifikant vermehrte Apoptoseresistenz auf und produzieren signifikant verstärkt „vascular endothelial growth factor“ (VEGF). Diese Übersichtsarbeit diskutiert die Ergebnisse der Preisträgerarbeit im aktuellen Kontext.

Abstract

Engraftment of mesenchymal stem cells (MSCs) has been proposed as a potential approach for the treatment of cardiac dysfunction. However, poor cell survival limits the regenerative capacity of this promising method. Following temporary overexpression of the anti-apoptotic gene BCL-2 in MSCs (BCL-MSCs) using a non-viral polymer-based gene transfer system, LAD (left anterior descending coronary artery) ligation in the rat experiment and subsequent injection of BCL-2-MSCs in the infarction border zone led to improvement of cell survival in vivo, significantly decreased infarction size, and enhanced capillary density. BCL-2-MSCs exhibit in vitro significantly higher resistance to apoptosis and produce significantly higher amounts of vascular endothelial growth factor (VEGF) under hypoxic conditions. The review discusses results from the award winning work in the current context.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3

Literatur

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Caplan AI (1994) The mesengenic process. Clin Plast Surg 21:429–435

    CAS  PubMed  Google Scholar 

  4. 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 

  5. da Silva Meirelles L, Caplan AI, Nardi NB (2008) In search of the in vivo identity of mesenchymal stem cells. Stem Cells 26:2287–2299

    Article  Google Scholar 

  6. da Silva Meirelles L, Chagastelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119:2204–2213

    Article  Google Scholar 

  7. Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403

    CAS  PubMed  Google Scholar 

  8. Furlani D, Li W, Pittermann E et al (2009) A transformed cell population derived from cultured mesenchymal stem cells has no functional effect after transplantation into the injured heart. Cell Transplant 18:319–331

    Article  PubMed  Google Scholar 

  9. 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 

  10. Javazon EH, Beggs KJ, Flake AW (2004) Mesenchymal stem cells: paradoxes of passaging. Exp Hematol 32:414–425

    Article  CAS  PubMed  Google Scholar 

  11. Kim S-J, Nasseri B, Lüders C, Kang K-S, Schmitt-Knosalla I, Hetzer R, Kurtz A, Stamm C (2009) Mesenchymal cord blood stem cells: A superior source for cardiac immunotherapy. In: 38. Jahrestagung der Deutschen Gesellschaft für Thorax-, Herz- und Gefäßchirurgie, Stuttgart. Abstract session basic science, V29

  12. Li W, Ma N, Ong LL, Nesselmann C, Klopsch C, Ladilov Y, Furlani D, Piechaczek C, Moebius JM, Lützow K, Lendlein A, Stamm C, Li RK, Steinhoff G (2007) BCL-2 Engineered MSCs Inhibited Apoptosis and Improved Heart Function. Stem Cells 25(8):2118-2127

    Article  CAS  PubMed  Google Scholar 

  13. 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  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  15. 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 9:1195–1201

    Article  CAS  PubMed  Google Scholar 

  16. McCulloch EA, Till JE (1960) The radiation sensitivity of normal mouse bone marrow cells, determined by quantitative marrow transplantation into irradiated mice. Radiat Res 13:115–125

    Article  CAS  PubMed  Google Scholar 

  17. Menasche P (2009) Stem cell therapy for heart failure: are arrhythmias a real safety concern? Circulation 119:2735–2740

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Schuleri KH, Boyle AJ, Hare JM (2007) Mesenchymal stem cells for cardiac regenerative therapy. Handb Exp Pharmacol 195–218

  20. Stamm C, Choi YH, Nasseri B, Hetzer R (2009) A heart full of stem cells: the spectrum of myocardial progenitor cells in the postnatal heart. Ther Adv Cardiovasc Dis 3:215–229

    Article  PubMed  Google Scholar 

  21. 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 133:717–725

    Article  PubMed  Google Scholar 

  22. 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 

  23. 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 

  24. Sutherland FW, Perry TE, Yu Y et al (2005) From stem cells to viable autologous semilunar heart valve. Circulation 111:2783–2791

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  27. Tse HF, Thambar S, Kwong YL 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 

  28. 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 

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

    Article  CAS  PubMed  Google Scholar 

  30. Yousef M, Schannwell CM, Kostering M et al (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 

  31. Yue WM, Liu W, Bi YW et al (2008) Mesenchymal stem cells differentiate into an endothelial phenotype, reduce neointimal formation, and enhance endothelial function in a rat vein grafting model. Stem Cells Dev 17:785–793

    Article  CAS  PubMed  Google Scholar 

Download references

Danksagungen

Diese Arbeit wurde von der Deutschen Helmholtz Gesellschaft, Mecklenburg Vorpommern (Nachwuchsgruppe Regenerative Medizin Regulation der Stammzellmigration 0402710), der Deutschen Forschungsgesellschaft, SFB/Transregio 37 und BMBF START-MSC unterstützt.

Interessenkonflikt

Die Autorin gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Klinik und Poliklinik für Herzchirurgie, Universität Rostock, Schillingallee 35, 18055, Rostock, Deutschland

    C. Neßelmann & G. Steinhoff

Authors
  1. C. Neßelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Steinhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Neßelmann.

Additional information

Auszugsweise Darstellung der aus der Preisträgerarbeit resultierenden und in Stem Cells [12] veröffentlichten Ergebnisse.

Representation of published results [12] in extracts, results from the award winning work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Neßelmann, C., Steinhoff, G. Mesenchymale Stammzellen zur kardialen Regeneration. Z Herz- Thorax- Gefäßchir 23, 383–387 (2009). https://doi.org/10.1007/s00398-009-0747-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00398-009-0747-4

Schlüsselwörter

Keywords

Search

Navigation