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Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium

Författare:
  • Eugen Kolossov
  • Toktam Bostani
  • Wilhelm Roell
  • Martin Breitbach
  • Frank Pillekamp
  • Jens Nygren
  • Philipp Sasse
  • Olga Rubenchik
  • Jochen W. U. Fries
  • Daniela Wenzel
  • Caroline Geisen
  • Ying Xia
  • Zhongju Lu
  • Yaqi Duan
  • Ralf Kettenhofen
  • Stefan Jovinge
  • Wilhelm Bloch
  • Heribert Bohlen
  • Armin Welz
  • Juergen Hescheler
  • Sten Eirik W Jacobsen
  • Bernd K. Fleischmann
Publiceringsår: 2006
Språk: Engelska
Sidor: 2315-2327
Publikation/Tidskrift/Serie: Journal of Experimental Medicine
Volym: 203
Nummer: 10
Dokumenttyp: Artikel
Förlag: Rockefeller University Press

Sammanfattning

Cellular cardiomyoplasty is an attractive option for the treatment of severe heart failure. It is, however, still unclear and controversial which is the most promising cell source. Therefore, we investigated and examined the fate and functional impact of bone marrow (BM) cells and embryonic stem cell (ES cell)-derived cardiomyocytes after transplantation into the infarcted mouse heart. This proved particularly challenging for the ES cells, as their enrichment into cardiomyocytes and their long-term engraftment and tumorigenicity are still poorly understood. We generated transgenic ES cells expressing puromycin resistance and enhanced green fluorescent protein cassettes under control of a cardiac-specific promoter. Puromycin selection resulted in a highly purified (> 99%) cardiomyocyte population, and the yield of cardiomyocytes increased 6-10-fold because of induction of proliferation on purification. Long-term engraftment (4-5 months) was observed when co-transplanting selected ES cell -derived cardiomyocytes and fibroblasts into the injured heart of syngeneic mice, and no teratoma formation was found (n = 60). Although transplantation of ES cell-derived cardiomyocytes improved heart function, BM cells had no positive effects. Furthermore, no contribution of BM cells to cardiac, endothelial, or smooth muscle neogenesis was detected. Hence, our results demonstrate that ES-based cell therapy is a promising approach for the treatment of impaired myocardial function and provides better results than BM-derived cells.

Disputation

Nyckelord

  • Medicine and Health Sciences

Övriga

Published
Yes
  • ISSN: 0022-1007

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