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Reprogrammation nucléaire de cardiomyocytes vers un stade progéniteur par fusion partielle avec des cellules souches adultes

Abstract : Regenerative cell therapy offers potential applications in many diseases involving cell loss. However, following myocardial infarction and the dramatic decrease in the number of cardiomyocytes, the injection of stem cells led to a poor and transient improvement of cardiac function. Therefore stem cell-based therapy to treat myocardial infarction requires a better understanding of the mechanisms brought into play by stem cells in heart regeneration. Among the different hypothesis raised, cell fusion between stem cells and cardiomyocytes has been described in several studies. However, the respective physiological impact of cell fusion remains unknown. During my thesis, I investigated this cell fusion mechanism in vitro in a coculture model between human multipotent adipose-derived stem cells (hMADS) and murine fully differentiated cardiomyocytes. We showed intercellular exchanges of cytoplasmic and nuclear material between both cell types, followed by a heterologous cell fusion process promoting cardiomyocyte reprogramming back to a progenitor-like state. The resulting hybrid cells expressed early cardiac commitment and proliferation markers and exhibited a mouse genotype. We provided evidence that cardiac hybrid cells were preferentially generated through partial cell fusion mediated by intercellular structures composed of f-actin and microtubule filaments. Furthermore, we showed that stem cell mitochondria were transferred into cardiomyocytes and were required for somatic cell reprogramming. In conclusion, by providing new insights into previously reported cell fusion processes, our results might contribute to a better understanding of stem cell-mediated regenerative mechanisms and thus, the development of more efficient stem cell-based heart therapies
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Submitted on : Monday, September 17, 2012 - 5:02:17 PM
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Adrien Acquistapace. Reprogrammation nucléaire de cardiomyocytes vers un stade progéniteur par fusion partielle avec des cellules souches adultes. Sciences agricoles. Université Paris-Est, 2011. Français. ⟨NNT : 2011PEST0078⟩. ⟨tel-00733068⟩

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