Three main themes are envisaged: - Study of MSC differentiation in follicular reticular cells (FRC), pericytes and/or myofibroblasts . FRC are mesenchymatous cells residing in the lymph nodes where they exert a potent regulatory activity on T lymphocytes. A better understanding of their biology and their relationship with MSC would help deciphering how they modulate T cells in situ, keeping in mind that such a control is pivotal for the maintenance of peripheral immune tolerance. - Investigation of the effect of MSC via the activation of indolamine 2,3, deoxygenase (IDO) upon tumor cell growth. IDO, through its ability to metabolize the essential amino acid L-tryptophan modulates many cell types, including T cells and several tumoral cells. The intensity of IDO censoring is related to cell sensitivity to tryptophan depletion. IDO direct effect is expected to inhibit tumor proliferation. However if a tumor becomes IDO-resistant and is surrounded by IDO+ cells, the depletion of tryptophan induced by IDO will inhibit tumor specific T cells and favor tumor growth. A better understanding of these processes should help the development of new aspects of anti-tumoral therapies. - Establishment of a protocol generating clinical grade MSC to be infused to patients suffering from severe GVHD. Many clinical trials suggest that MSC systemic infusion may stop steroid resistant GVHD. However the paucity of GMP grade MSC often prejudices the initiation of such treatment. This project consists in the finalization of the production of MSC in white room conditions.

Nephrology