Impact of in vitro expansion on immunomodulation properties of mesenchymal stromal cells

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Charif, Naceur | El Ouafy, Meriem | Ghannoum, Dima | Notarantonio, Anne-Béatrice | Li, Yinping | Cauchois, Ghislaine | Stoltz, Jean-François | Rubio, Marie Therese | de Isla, Natalia

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International audience. Mesenchymal Stromal/Stem Cells (MSC) are a heterogeneous population of self-renewal multipotent cells which can be obtained from adult sources (Bone Marrow MSC (BM-MSC)) and fetal sources (Wharton Jelly MSC (WJ-MSC)). MSC are a very interesting tool for cell engineering because of their differentiation properties and for cell therapy because of their immunomodulation properties. Indeed, MSC secrete soluble factors which can modulate the immune response.Before their clinical use an in vitro expansion step must be performed in order to obtain the sufficient dose (106 à 107 cells/kilogram of human body weight). During this expansion step, MSC are subjected to physical-chemical strain which could induce changes in their quality (senescence) and in their functional properties (migration, immunomodulation) and could affect the therapeutic efficacy.In our previous work we studied the impact of culture conditions (normoxia, hypoxia, fetal calf serum (FCS) supplement, human platelet lysate (h-PL) supplement on the behavior of MSC and we showed that a better proliferation was obtained when MSC were expanded with human platelet lysate (h-PL) in hypoxia for WJ-MSC and in normoxia for BM-MSC.The aim of this work was to study the impact of in vitro expansion on MSC immunomodulation properties. Our results showed that WJ and BM-MSC expanded in hypoxia have better immunomodulation properties and that senescence and interferon-γ (IFN-γ) stimulation could affect the MSC immunomodulation properties.To explain this results, it would be interesting to know if there is a link between the expression of surface markers implicated in immunomodulation and MSC immunomodulatory properties.

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