Xiong Qing-Hua, Zhao Lei, Wan Guan-Qun, Hu Yun-Gang, Li Xiao-Lin
Department of Plastic and Maxillofacial Surgery, Jiangxi Provincial People's Hospital/Jiangxi Province Key Laboratory of Maxillofacial Plastic and Reconstruction, Nanchang, China.
Endocr Metab Immune Disord Drug Targets. 2023;23(3):336-346. doi: 10.2174/1871530322666220523151713.
The healing of cutaneous wounds requires better strategies, which remain a challenge. Previous reports indicated that the therapeutic function of mesenchymal stem cells is mediated by exosomes. This work demonstrated the regenerative effects of engineered BMSCsderived Exosomal miR-542-3p in skin wound mouse models.
Bone marrow mesenchymal stem cells (BMSCs) -derived exosomes (BMSCs-Exos) were isolated by ultracentrifugation and identified by Transmission Electron Microscope (TEM) and Nanoparticle Tracking Analysis (NTA). BMSCs-Exo was loaded with miRNA-542-3p by electroporation. We explored the effects of miRNA-542-3p-Exo on the proliferation and migration of Human Skin Fibroblasts (HSFs)/Human dermal microvascular endothelial cells (HMECs). In addition, The angiogenesis of HMECs was detected by Tube formation assay in vitro. The effects of miRNA-542-3p-Exo in the skin wound mouse model were detected by H&E staining, Masson staining, and immunofluorescence analysis. We assessed the effect of miRNA-542-3p-Exo on collagen deposition, new blood vessel formation, and wound remodeling in a skin wound mouse model.
MiRNA-542-3p-Exos could be internalized by HSFs/HMECs and enhance the proliferation, migration, and angiogenesis of HSFs/HMECs in vitro and in vivo. The protein expression of collagen1/3 was significantly increased after miRNA-542-3p-Exo treatment in HSFs. In addition, the local injection of miRNA-542-3p-Exo promoted cellular proliferation, collagen deposition, neovascularization, and accelerated wound closure.
This study suggested that miRNA-542-3p-Exo can stimulate HSFs/HMECs function. The treatment of miRNA-542-3p-Exo in the skin wound mouse model significantly promotes wound repair. The therapeutic potential of miRNA-542-3p-Exo may be a future therapeutic strategy for cutaneous wound healing.
皮肤伤口的愈合需要更好的策略，这仍然是一个挑战。先前的报道表明，间充质干细胞的治疗功能是由外泌体介导的。本研究证实了工程化骨髓间充质干细胞来源的外泌体miR-542-3p在皮肤伤口小鼠模型中的再生作用。
通过超速离心法分离骨髓间充质干细胞（BMSCs）来源的外泌体（BMSCs-Exos），并通过透射电子显微镜（TEM）和纳米颗粒跟踪分析（NTA）进行鉴定。通过电穿孔法将miRNA-542-3p载入BMSCs-Exo。我们探讨了miRNA-542-3p-Exo对人皮肤成纤维细胞（HSFs）/人真皮微血管内皮细胞（HMECs）增殖和迁移的影响。此外，通过体外管腔形成实验检测HMECs的血管生成情况。通过苏木精-伊红染色（H&E）、Masson染色和免疫荧光分析检测miRNA-542-3p-Exo在皮肤伤口小鼠模型中的作用。我们评估了miRNA-542-3p-Exo对皮肤伤口小鼠模型中胶原沉积、新血管形成和伤口重塑的影响。
miRNA-542-3p-Exos可被HSFs/HMECs内化，并在体内外增强HSFs/HMECs的增殖、迁移和血管生成。miRNA-542-3p-Exo处理后，HSFs中胶原1/3的蛋白表达显著增加。此外，局部注射miRNA-542-3p-Exo可促进细胞增殖、胶原沉积、新血管形成，并加速伤口闭合。
本研究表明，miRNA-542-3p-Exo可刺激HSFs/HMECs的功能。在皮肤伤口小鼠模型中，miRNA-542-3p-Exo治疗可显著促进伤口修复。miRNA-542-3p-Exo的治疗潜力可能是皮肤伤口愈合的未来治疗策略。
