Immunomodulatory properties of human MuStem cells: assessing their impact on adaptive and innate immunity
Résumé
Several preclinical approaches based on allogeneic stem cell delivery were shown to be attractive for the treatment of genetic muscular dystrophies. Nevertheless, a significant hurdle for their clinical translation is the immune rejection of donor cells. Immunosuppressive regimens are generally used to overcome host immunity and can allow the improvement of graft survival. Nevertheless, they are associated with a number of side effects, limiting their long term use. Recently, some tissue-specific adult stem cell populations were described to exhibit immunomodulatory properties that could increase their ability to engraft in an allogeneic recipient and improve their regenerative potential. We have previously demonstrated that allogeneic muscle-derived delayed adherent stem cells (that we called MuStem cells) are able to phenotypically and clin- ically correct the Duchenne dystrophic canine model (Rouger et al., 2011; Robriquet et al., 2015). Recently, we isolated human MuStem cells and assessed their immunomodulatory potential. We evaluated their ability to inhibit T cell prolif- eration and to modulate the complement pathway. Interest- ingly, our preliminary data showed that human MuStem cells were able to modulate allogeneic T cell proliferation and to express immunomodulatory molecules such as prostaglandin- E2, indoleamin-2,3-deoxygenase-1 and TGFb2. Moreover, MuStem cells were also able to secrete Factor H molecule suggesting a potential effect on the alternate pathway of the complement system. Overall, our study is critical for the un- derstanding of the crosstalk between MuStem cells and the im- mune system, as well as the design of safe and efficient allogeneic stem cell-based therapy for the treatment of muscle dystrophies
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