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 Disclosure of potential conflicts of interest is found at the end of this article.

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Background-The outcome of resuscitated patients after cardiac arrest complicating acute myocardial infarction remains poor, primarily because of the relatively low success rates of cardiopulmonary resuscitation management. Existing data suggest potential beneficial effects of early myocardial reperfusion, but the predictors of survival in these patients remain unknown. Methods and Results-From 1995 to 2005, 186 patients (78% men; mean age, 60.4Ϯ13.8 years) underwent immediate percutaneous coronary intervention after successful resuscitation for cardiac arrest complicating acute myocardial infarction. Prompt prehospital management was performed by mobile medical care units in 154 of 186 patients, whereas 32 had in-hospital cardiac arrest. Infarct location was anterior in 105 patients (56%), and shock was present on admission in 96 (52%). Percutaneous coronary intervention (stenting rate 90%) was successful in 161 of 186 patients (87%). Six-month survival rate was 100 of 186 (54%), and 6-month survival free of neurological sequelae was 46%. By multivariate analysis, predictors of 6-month survival were a shorter interval between the onset of cardiac arrest and arrival of a first responder (odds ratio, 0.67; 95% CI, 0.54 to 0.84), a shorter interval between the onset of cardiac arrest and return of spontaneous circulation (odds ratio, 0.91; 95% CI, 0.87 to 0.96), and absence of diabetes (odds ratio, 7.30; 95% CI, 1.80 to 29.41). Conclusions-In patients with resuscitated cardiac arrest complicating acute myocardial infarction, prompt prehospital management and early revascularization were associated with a 54% survival rate at 6 months. A strategy including adequate prehospital management, early revascularization, and specific care in dedicated intensive care units should be strongly considered in resuscitated patients after cardiac arrest complicating acute myocardial infarction. (Circulation.