Abstract
As a potential clinical therapeutic cell for injured tissue repair, mesenchymal stem cells (MSCs) have attracted increasing attention. Enhancing the pro-healing function of MSCs has gradually become an essential topic in improving the clinical efficacy of MSCs. Recently, studies have shown that neuronal protein 3.1 (P311) plays a crucial role in promoting skin wound healing, suggesting P311 gene modification may improve the pro-healing function of MSCs. In this study, we demonstrated that increasing the in vivo expression of P311 could significantly enhance the ability of MSCs to lessen the number of inflammatory cells, increase the expression of IL10, reduce the levels of TNF-α and IFN-γ, increase collagen deposition, promote angiogenesis, and ultimately accelerate skin wound closure and improve the quality of wound healing. Importantly, we uncovered that P311 enhanced the pro-angiogenesis function of MSCs by increasing the production of vascular endothelial growth factor (VEGF) in vitro and in vivo. Mechanistically, we revealed that the mTOR signalling pathway was closely related to the regulation of P311 on VEGF production in MSCs. Together, our data displayed that P311 gene modification in MSCs augments their capabilities to promote skin wound closure, which might bring the dawn for its clinical application in the future.
Highlights
Skin wounds caused by various injuries, such as trauma, burns and diabetes mellitus, are a current clinical problem in urgent need of solutions
Previous studies demonstrated that P311 plays essential regulatory roles in skin wound healing, while exogenous administration of mesenchymal stem cells (MSCs) was beneficial to skin wound repair [12, 23]
The results showed the positive expression for CD29, CD44 and CD90, and negative expression for CD11B (Supplementary Figure 1A), and differentiation into osteocytes and adipose cells (Supplementary Figure 1B), suggesting the expanded MSCs were of sound purity
Summary
Skin wounds caused by various injuries, such as trauma, burns and diabetes mellitus, are a current clinical problem in urgent need of solutions. We demonstrated that P311 induced the trans-differentiation of epidermal stem cells to myofibroblast-like cells by stimulating transforming growth factor b1 (TGFb) expression for accelerating wound repair; loss of P311 attenuates angiogenesis in cutaneous wound healing [14]. These studies have shed light on the role of P311 in functioning myofibroblast differentiation, angiogenesis, and re-epithelialisation after cutaneous injury; the effect of P311 on the pro-healing function of MSCs has not yet been well-elucidated
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