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

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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; Sasse, Philipp; Rubenchik, Olga; Fries, Jochen W. U.; Wenzel, Daniela; Geisen, Caroline; Xia, Ying; Lu, Zhongju; Duan, Yaqi; Kettenhofen, Ralf; Jovinge, Stefan; Bloch, Wilhelm; Bohlen, Heribert; Welz, Armin; Hescheler, Juergen; Jacobsen, Sten Eirik W; Fleischmann, Bernd K.

In: Journal of Experimental Medicine, Vol. 203, No. 10, 2006, p. 2315-2327.

Research output: Contribution to journalArticle

Harvard

Kolossov, E, Bostani, T, Roell, W, Breitbach, M, Pillekamp, F, Nygren, J, Sasse, P, Rubenchik, O, Fries, JWU, Wenzel, D, Geisen, C, Xia, Y, Lu, Z, Duan, Y, Kettenhofen, R, Jovinge, S, Bloch, W, Bohlen, H, Welz, A, Hescheler, J, Jacobsen, SEW & Fleischmann, BK 2006, 'Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium', Journal of Experimental Medicine, vol. 203, no. 10, pp. 2315-2327. https://doi.org/10.1084/jem.20061469

APA

Kolossov, E., Bostani, T., Roell, W., Breitbach, M., Pillekamp, F., Nygren, J., ... Fleischmann, B. K. (2006). Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium. Journal of Experimental Medicine, 203(10), 2315-2327. https://doi.org/10.1084/jem.20061469

CBE

Kolossov E, Bostani T, Roell W, Breitbach M, Pillekamp F, Nygren J, Sasse P, Rubenchik O, Fries JWU, Wenzel D, Geisen C, Xia Y, Lu Z, Duan Y, Kettenhofen R, Jovinge S, Bloch W, Bohlen H, Welz A, Hescheler J, Jacobsen SEW, Fleischmann BK. 2006. Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium. Journal of Experimental Medicine. 203(10):2315-2327. https://doi.org/10.1084/jem.20061469

MLA

Vancouver

Author

Kolossov, Eugen ; Bostani, Toktam ; Roell, Wilhelm ; Breitbach, Martin ; Pillekamp, Frank ; Nygren, Jens ; Sasse, Philipp ; Rubenchik, Olga ; Fries, Jochen W. U. ; Wenzel, Daniela ; Geisen, Caroline ; Xia, Ying ; Lu, Zhongju ; Duan, Yaqi ; Kettenhofen, Ralf ; Jovinge, Stefan ; Bloch, Wilhelm ; Bohlen, Heribert ; Welz, Armin ; Hescheler, Juergen ; Jacobsen, Sten Eirik W ; Fleischmann, Bernd K. / Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium. In: Journal of Experimental Medicine. 2006 ; Vol. 203, No. 10. pp. 2315-2327.

RIS

TY - JOUR

T1 - Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium

AU - Kolossov, Eugen

AU - Bostani, Toktam

AU - Roell, Wilhelm

AU - Breitbach, Martin

AU - Pillekamp, Frank

AU - Nygren, Jens

AU - Sasse, Philipp

AU - Rubenchik, Olga

AU - Fries, Jochen W. U.

AU - Wenzel, Daniela

AU - Geisen, Caroline

AU - Xia, Ying

AU - Lu, Zhongju

AU - Duan, Yaqi

AU - Kettenhofen, Ralf

AU - Jovinge, Stefan

AU - Bloch, Wilhelm

AU - Bohlen, Heribert

AU - Welz, Armin

AU - Hescheler, Juergen

AU - Jacobsen, Sten Eirik W

AU - Fleischmann, Bernd K.

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1084/jem.20061469

DO - 10.1084/jem.20061469

M3 - Article

VL - 203

SP - 2315

EP - 2327

JO - Journal of Experimental Medicine

T2 - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 1540-9538

IS - 10

ER -