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Conglomeration of T- and B-Cell Matrix Responses Determines the Potency of Human Bone Marrow Mesenchymal Stromal Cells. Stem Cells 2022 Dec 31;40(12):1134-1148



Pubmed ID




Scopus ID

2-s2.0-85145424751 (requires institutional sign-in at Scopus site)   3 Citations


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 action in humans is not well defined, more than a single functional property of MSCs needs 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 is 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 fulfills the potency assay matrix strategy by incorporating MSCs' interaction with more than a single inflammatory immune responder.

Author List

Porter AP, Pirlot BM, Dyer K, Uwazie CC, Nguyen J, Turner C, Rajan D, Hematti P, Chinnadurai R


Peiman Hematti MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Bone Marrow
Bone Marrow Cells
Cell Proliferation
Coculture Techniques
Leukocytes, Mononuclear