Cyclosporine A and IFNγ licencing enhances human mesenchymal stromal cell potency in a humanised mouse model of acute graft versus host disease

Abstract Immunosuppressive ability in human MSC donors has been shown to be variable and may a limiting factor therapeutic efficacy vivo. The importance of cytokine activation mesenchymal stromal cells (MSCs) facilitate their immunosuppressive function is well established. This study sought further understand the interactions between MSCs commonly used calcineurin inhibitor cyclosporine A (CsA). existing literature regarding approaches that use are conflicting effect CsA on potency function. Here, we clearly demonstrate when added at same time as MSCs, negatively affects suppression T cell proliferation. However, licencing with IFNγ before addition protects from this negative effect. Notably, adding after pre-stimulation enhances production IDO. Mechanistically, identified reduces SOCS1 expression enhanced IDO pre-stimulated MSCs. Importantly, exposure administration, significantly relevant humanised mouse model acute Graft versus Host Disease. In summary, novel strategy enhance vitro