z-logo
open-access-imgOpen Access
Human Mesenchymal Stem Cells Reprogram Adult Cardiomyocytes Toward a Progenitor‐Like State Through Partial Cell Fusion and Mitochondria Transfer
Author(s) -
Acquistapace Adrien,
Bru Thierry,
Lesault PierreFrançois,
Figeac Florence,
Coudert Amélie E.,
le Coz Olivier,
Christov Christo,
Baudin Xavier,
Auber Fréderic,
Yiou René,
DuboisRandé JeanLuc,
Rodriguez AnneMarie
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.632
Subject(s) - biology , microbiology and biotechnology , stem cell , reprogramming , cell fusion , induced stem cells , progenitor cell , cellular differentiation , adult stem cell , cell potency , endothelial stem cell , multipotent stem cell , mesenchymal stem cell , induced pluripotent stem cell , cell , embryonic stem cell , genetics , gene , in vitro
Abstract 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. S TEM C ELLS 2011;29:812–824

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here