Abstract

Immune Modulation by Mesenchymal Stem Cells through Extracellular Vesicles

Andrew Hoffman, Professor, Director -- Regenerative Medicine Laboratory, Tufts University

Mesenchymal stem cells (MSC) are currently being evaluated in human clinical trials for their potential to mitigate injuries due to inflammatory, ischemic or hyperoxic, pro-fibrotic, septic, degenerative, and neoplastic insults.   The MSC are employed as either native, pre-conditioned, or genetically manipulated cells, or they are exogenously supplemented biologic or pharmacologic agents (e.g. chemotherapeutics).   The mechanisms employed by MSC in vivo have come into question, with the realization that MSC are short-lived in vivo, and factors such as extracellular vesicles (EV) exert interactions with resident immune effector.   Better understanding of immune mechanisms of native EV will lead to superior MSC selection and preparation for therapeutic purposes.  We report that EV from umbilical cord tissue Wharton’s Jelly MSC participate in signaling networks such as TGF-B and adenosine previously attributed to non-EV soluble mediators.   The biological activity of EV-associated TGF-B which is packaged into EV membranes as latent or pro-forms, requires activation through bystander proteases and effector cells (e.g. monocytes) present in biofluids, presenting a complex interaction.   How these observations impact the conduct and interpretation of standard immune assays, and the implications for improving MSC for therapeutic applications is discussed.