059b7b9a20ec0a2c7ddae9656a1b8c16 pmc_32942629.pdf f843a6ecdc051aab105e4fdcc1a5137fbf78bc45 pmc_32942629.pdf 14a865024f8380f5b035b356e8d9f06a3c619956bb54e2bb4f7097572b635899 pmc_32942629.pdf Title: Potential of Extracellular Vesicle-Associated TSG-6 from Adipose Mesenchymal Stromal Cells in Traumatic Brain Injury Subject: Multipotent mesenchymal stromal cells (MSC) represent a promising strategy for a variety of medical applications. Although only a limited number of MSC engraft and survive after in vivo cellular infusion, MSC have shown beneficial effects on immunomodulation and tissue repair. This indicates that the contribution of MSC exists in paracrine signaling, rather than a cell-contact effect of MSC. In this review, we focus on current knowledge about tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) and mechanisms based on extracellular vesicles (EV) that govern long-lasting immunosuppressive and regenerative activity of MSC. In this context, in particular, we discuss the very robust set of findings by Jha and colleagues, and the opportunity to potentially extend their research focus on EV isolated in concentrated conditioned media (CCM) from adipose tissue derived MSC (ASC). Particularly, the authors showed that ASC-CCM mitigated visual deficits after mild traumatic brain injury in mice. TSG-6 knockdown ASC were, then, used to generate TSG-6-depleted CCM that were not able to replicate the alleviation of abnormalities in injured animals. In light of the presented results, we envision that the infusion of much distilled ASC-CCM could enhance the alleviation of visual abnormalities. In terms of EV research, the advantages of using size-exclusion chromatography are also highlighted because of the enrichment of purer and well-defined EV preparations. Taken together, this could further delineate and boost the benefit of using MSC-based regenerative therapies in the context of forthcoming clinical research testing in diseases that disrupt immune system homeostasis. Keywords: conditioned medium; extracellular vesicles; immunomodulation; mesenchymal stromal cells; traumatic brain injury; paracrine function; regenerative medicine; tissue repair; translational medicine; tumor necrosis factor-stimulated gene-6 Author: Santiago Roura, Marta Monguió-Tortajada, Micaela Munizaga-Larroudé, Marta Clos-Sansalvador, Marcella Franquesa, Anna Rosell and Francesc E. 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