Conglomeration of T and B Cell Matrix Responses Determines the Potency of Human Bone Marrow Mesenchymal Stromal Cells.

Cell manufacturing facilities need to define the potency of Mesenchymal Stromal Cells (MSCs) as cellular therapeutics in advanced clinical trials or marketing approval. Since MSCs' mechanism of actions in humans are not well defined, more than a single functional property of MSCs need to be captured as a surrogate measure of potency utilizing assay matrix technologies. However, the current limitation is the sole investigation of MSC mediated T cell suppression as a surrogate measure of potency. We investigated the effect of MSCs on B cell matrix responses to be incorporated into the assay matrix potency analytical system. Our results demonstrate that MSCs inhibit B cell differentiation and block pan-antibody secretion upon activation of B cells in the PBMCs. In contrast, MSCs are inferior in blocking B cell matrix responses when purified B cells are used. Mechanistic analysis has demonstrated that MSC mediated inhibition of B cell matrix responses are non-contact dependent and Tryptophan metabolic pathway plays a major role, akin to the mechanism of MSC mediated T cell suppression. MSCs also inhibit both T cell and B cell responses when both of these lymphoid populations are concurrently activated in the PBMCs. Secretome analysis of MSC and T/B cell activated PBMC cocultures identified direct and inverse correlative matrix signatures between humoral antibody isotypes and secretory molecules. The current analysis of the combined and concomitant investigation of T cell and B cell matrix responses fulfil the potency assay matrix strategy by incorporating MSCs' interaction with more than a single inflammatory immune responder.