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Contribution au développement d’un produit de thérapie cellulaire à base de cellules stromales mésenchymateuses : effet de l’environnement et recherche de marqueurs de qualité

Abstract : Mesenchymal Stromal/Stem Cells (MSC) are a heterogeneous population present in adult and fetal tissues. They are interesting in regenerative medicine for their differentiation and immunomodulation properties via the secretion of soluble factors that modulate the immune response. An in vitro expansion step is necessary to obtain enough cells for clinical applications, which can affect the MSC quality and must be controlled to maintain their therapeutic efficacy. The first objective of this thesis was to study the impact of culture conditions (normoxia, hypoxia, fetal calf serum (FCS) or human platelet lysate (HPL) as a culture supplement) on the behavior and functionality of Wharton's jelly (WJ-MSC) and bone marrow (BM-MSC) MSC. We showed that MSC cultured in the presence of HPL have better clonogenic and proliferative properties with low senescence. Moreover, culture in hypoxia improves immuosuppressive properties and amplifies the effect of LPH on migration properties. The second objective was to find quality markers related to proliferation. We have shown that miR-9 is associated with low proliferation capacities of WJ-MSC and BM-MSC. Further experiments should be performed to confirm that this marker is predictive of MSC quality. The third objective was to study the impact of oxidative stress and inflammatory context on WJ-MSC functionality. We have shown that hydrogen peroxide (H2O2) induces senescence of WJ-MSC which alters their migration and immunosuppression properties. To conclude WJ-MSC and BM-MSC expanded in hypoxia with HPL are less senescent and have better proliferation, migration and immunosuppression properties. Nevertheless, further experiments need to be performed to understand the involvement of ROS in the MSC immunosuppressive properties.
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https://hal.univ-lorraine.fr/tel-03387813
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Submitted on : Wednesday, October 20, 2021 - 8:47:39 AM
Last modification on : Thursday, October 21, 2021 - 5:32:32 AM

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  • HAL Id : tel-03387813, version 1

Citation

Naceur Charif. Contribution au développement d’un produit de thérapie cellulaire à base de cellules stromales mésenchymateuses : effet de l’environnement et recherche de marqueurs de qualité. Sciences du Vivant [q-bio]. Université de Lorraine, 2021. Français. ⟨NNT : 2021LORR0125⟩. ⟨tel-03387813⟩

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