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

Kolossov, Eugen; Bostani, Toktam; Roell, Wilhelm; Breitbach, Martin; Pillekamp, Frank; Nygren, Jens LU ; Sasse, Philipp; Rubenchik, Olga; Fries, Jochen W. U. and Wenzel, Daniela, et al. (2006) In Journal of Experimental Medicine 203(10). p.2315-2327
Abstract
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... (More)
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. (Less)
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publication status
published
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Journal of Experimental Medicine
volume
203
issue
10
pages
2315 - 2327
publisher
Rockefeller University Press
external identifiers
  • wos:000240951400019
  • scopus:33749367585
ISSN
1540-9538
DOI
10.1084/jem.20061469
language
English
LU publication?
yes
id
ed32ecaf-d7e8-410b-affc-a5ae78cd8aad (old id 389540)
date added to LUP
2007-10-07 16:55:27
date last changed
2019-05-21 02:46:26
@article{ed32ecaf-d7e8-410b-affc-a5ae78cd8aad,
  abstract     = {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.},
  author       = {Kolossov, Eugen and Bostani, Toktam and Roell, Wilhelm and Breitbach, Martin and Pillekamp, Frank and Nygren, Jens and Sasse, Philipp and Rubenchik, Olga and Fries, Jochen W. U. and Wenzel, Daniela and Geisen, Caroline and Xia, Ying and Lu, Zhongju and Duan, Yaqi and Kettenhofen, Ralf and Jovinge, Stefan and Bloch, Wilhelm and Bohlen, Heribert and Welz, Armin and Hescheler, Juergen and Jacobsen, Sten Eirik W and Fleischmann, Bernd K.},
  issn         = {1540-9538},
  language     = {eng},
  number       = {10},
  pages        = {2315--2327},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium},
  url          = {http://dx.doi.org/10.1084/jem.20061469},
  volume       = {203},
  year         = {2006},
}