Caractérisation des progéniteurs cellulaires exprimant les aldéhydes déshydrogénases (ALDH) dans des modèles sains et dystrophiques

Abstract : Cell therapy is a regenerative medicine strategy considered for the treatment of cardiac or skeletal muscle diseases. The cellular progenitors used to date (myoblasts or mesenchymal stem cells) provided mitigated success, thus mandating the identification and characterization of new categories of progenitors. Our laboratory has identified new populations of progenitors, based on their Aldehyde Deshydrogenase activity (ALDH) detectable using the fluorescent substrate Aldefluor, associated with the expression of the CD34 marker. ALDH are involved in metabolism and detoxification of aldehydes, they play important roles in cell survival and differentiation and are considered a new marker of stem cells. The present project allowed characterizing extensively the myogenic (ALDH+/CD34-) and non myogenic (ALDH+/CD34+) progenitors, in several physiopathological contexts and animal models. The presence of ALDH+/CD34- cells in distinct muscle groups in Human and non-human Primates, their persistence through natural ageing and despite the ongoing degenerative process observed in Duchenne muscular dystrophy in Human patients and animal models suggest their future use for therapeutic applications. The phenotypic characterization indicated that membrane markers are associated to myogenic or non myogenic sub-populations of ALDH cells. The comparison on their efficacies in vito and in vivo will allow proposing new candidates for cell therapy. In parallele, histological and cytological analysis identified cell populations expressing isoenzymes The analysis of gene expressions suggested that, at least, some of them are involved in muscle homeostasis in situ or in vitro.
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Jessy Etienne. Caractérisation des progéniteurs cellulaires exprimant les aldéhydes déshydrogénases (ALDH) dans des modèles sains et dystrophiques. Biologie cellulaire. Université Pierre et Marie Curie - Paris VI, 2016. Français. ⟨NNT : 2016PA066721⟩. ⟨tel-01618536⟩



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