Transplantation of Umbilical Cord-Derived Mesenchymal Stem Cells Attenuates Surgical Wound-Induced Blood-Brain Barrier Dysfunction in Mice

脐带间充质干细胞移植可减轻小鼠手术伤口引起的血脑屏障功能障碍

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Abstract

Blood-brain barrier (BBB) is the most important component of central nervous system (CNS) to keep toxins and pathogens from CNS. Although our studies demonstrated that using interleukin-6 antibodies (IL-6-AB) reversed the increased permeability of BBB, IL-6-AB is limited in their application that only could be used a few hours before surgery and seemed delayed the surgical wounds healing process, which urges us to find another more effective method. In this study, we employed the C57BL/6J female mice to investigate the potential effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation on BBB dysfunction induced by surgical wound. Compared to IL-6-AB, the transplantation of UC-MSCs more effectively decreased the BBB permeability after surgical wound evaluated by dextran tracer (immunofluorescence imaging and luorescence quantification). In addition, UC-MSCs can largely decrease the ratio of proinflammatory cytokine IL-6 to the anti-inflammatory cytokine IL-10 in both serum and brain tissue after surgical wound. Moreover, UC-MSCs successfully increased the levels of tight junction proteins (TJs) in BBB such as ZO-1, Occludin, and Claudin-5 and extremely decreased the level of matrix metalloproteinase-9 (MMP-9). Interestingly, UC-MSCs treatment also had positive effects on wound healing while protecting the BBB dysfunction induced by surgical wound compared to IL-6-AB treatment. These findings suggest that UC-MSCs transplantation is a highly efficient and promising approach on protecting the integrity of BBB which caused by peripheral traumatic injuries.

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