Potential of Extracellular Vesicle-Associated TSG-6 from Adipose Mesenchymal Stromal Cells in Traumatic Brain Injury

Abstract

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.

Mesenchymal Stem Cell-Derived Exosomes as New Remedy for the Treatment of Neurocognitive Disorders

“…During the past decade, a large number of experimental studies provided evidence about beneficial effects of MSC-Exos in the treatment of Alzheimer disease, Parkinson disease, post-traumatic and ischemic brain injury, schizophrenia, and autism spectrum disorders (ASD) ( Table A1 ) [ 12 , 13 , 14 , 15 , 16 , 17 ]. In this review article, we emphasized their findings, indicating MSC-Exos as potentially new therapeutic agents for the treatment of neurocognitive diseases.…”

IL-10 Mediated Immunomodulation Limits Subepithelial Fibrosis and Repairs Airway Epithelium in Rejecting Airway Allografts

“…TSG-6 has been associated with the regulation of pro-inflammatory cytokines and the augmentation of tissue repair in various animal models while suppressing inflammatory reactions triggered by ischemia in the heart and thereby limiting the destruction of cardiomyocytes [ 48 , 52 , 53 , 54 , 55 , 84 ]. TSG-6 gene inactivation has been associated with the upregulation of inflammatory immune reactions, while the over-expression of the TSG-6 gene has been associated with the downregulation of inflammatory reactions [ 85 , 86 ].…”

Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine

“…Impacts from sports, car crashes, military experiences, or falls can lead to damage to the brain called a concussion, or traumatic brain injury (TBI). Originally thought to be an acute event, research has now shown that TBIs can lead to long-lasting effects on brain function, reducing life expectancy [308,309,314]. TBIs produce immediate trauma to the brain in which neurons, glia, and blood vessels stretch or tear, inducing apoptosis and damaging the BBB.…”