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L'effet de l'hypoxie sur les conditions de culture des cellules souches mésenchymateuses de la moelle osseuse

Abstract : It is now settled that mesenchymal stem cells (MSC), reside in the same microenvironment or niche than hematopoietic stem cells (HSC), within the bone marrow (BM). It is also known that the O2 tension (pO2) of the niche is below 5% as compared to 21% O2 in the air and 12-15% in the arterial blood. As developed in our recent review, this physiological hypoxia protects stem cells from oxidative stress and maintains their multipotential state. Our hypothesis is that MSC cultured in hypoxia should be closer to their physiological condition and therefore more "multipotent". MSC from human BM were cultured et 21% and at 5% pO2. Their morphology, their ability to differentiate into osteocytes and adipocytes, and their transcriptome were compared at different passages. We observed a decrease of proliferation rate in early times in hypoxia, characterized by inhibition of the expression of genes involved in cell replication and cell cycle, and an increase in later passages. Whatever the passage, the genes encoding adhesion molecules and extracellular matrix are stimulated by hypoxia. At later times, the ability of MSC differentiation is stimulated by hypoxia, the cells look to be more immature and show decreased synthesis of mitochondria. Indeed, hypoxia stimulates the synthesis of plasticity genes according to "Gene Ontology" (GO) terms, and of several genes involved in neuronal- and epithelial-cell development. In conclusion, the culture of MSC from BM in hypoxia seems to be more physiological and may be useful for regenerative medicine applications.
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Submitted on : Thursday, March 29, 2018 - 10:28:50 AM
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Leticia Basciano. L'effet de l'hypoxie sur les conditions de culture des cellules souches mésenchymateuses de la moelle osseuse. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2011. Français. ⟨NNT : 2011NAN10100⟩. ⟨tel-01746247⟩



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