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Version of Record online: 19 APR 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 5, pages 812–824, May 2011
How to Cite
Acquistapace, A., Bru, T., Lesault, P.-F., Figeac, F., Coudert, A. E., le Coz, O., Christov, C., Baudin, X., Auber, F., Yiou, R., Dubois-Randé, J.-L. and Rodriguez, A.-M. (2011), Human Mesenchymal Stem Cells Reprogram Adult Cardiomyocytes Toward a Progenitor-Like State Through Partial Cell Fusion and Mitochondria Transfer. STEM CELLS, 29: 812–824. doi: 10.1002/stem.632
Author contributions: A.A., T.B., and A.M.R.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; P.F.L., F.F., A.E.C., and O.L.C.: collection and assembly of data, data analysis and interpretation; C.C. and X.B.: collection and assembly of data; F.A.: provision of study material or patients; R.Y.: conception and design, final approval of manuscript; J.L.D.: financial support, conception and design, final approval of manuscript. A.A. and T.B. contributed equally to this article.
First published online in STEM CELLS EXPRESS March 23, 2011.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue online: 19 APR 2011
- Version of Record online: 19 APR 2011
- Accepted manuscript online: 23 MAR 2011 04:21PM EST
- Manuscript Accepted: 3 MAR 2011
- Manuscript Received: 26 OCT 2010
- Mesenchymal stem cells;
- Cell fusion;
- Nuclear reprogramming
Because stem cells are often found to improve repair tissue including heart without evidence of engraftment or differentiation, mechanisms underlying wound healing are still elusive. Several studies have reported that stem cells can fuse with cardiomyocytes either by permanent or partial cell fusion processes. However, the respective physiological impact of these two processes remains unknown in part because of the lack of knowledge of the resulting hybrid cells. To further characterize cell fusion, we cocultured mouse fully differentiated cardiomyocytes with human multipotent adipose-derived stem (hMADS) cells as a model of adult stem cells. We found that heterologous cell fusion promoted cardiomyocyte reprogramming back to a progenitor-like state. The resulting hybrid cells expressed early cardiac commitment and proliferation markers such as GATA-4, myocyte enhancer factor 2C, Nkx2.5, and Ki67 and exhibited a mouse genotype. Interestingly, human bone marrow-derived stem cells shared similar reprogramming properties than hMADS cells but not human fibroblasts, which suggests that these features might be common to multipotent cells. Furthermore, cardiac hybrid cells were preferentially generated by partial rather than permanent cell fusion and that intercellular structures composed of f-actin and microtubule filaments were involved in the process. Finally, we showed that stem cell mitochondria were transferred into cardiomyocytes, persisted in hybrids and were required for somatic cell reprogramming. In conclusion, by providing new insights into previously reported cell fusion processes, our data might contribute to a better understanding of stem cell-mediated regenerative mechanisms and thus, the development of more efficient stem cell-based heart therapies. STEM CELLS 2011;29:812–824