Jian Xichao, Han Jiansu, Liu Xin, Deng Yaping, Gao Shaoying, Xiao Shune, Zhang Yan, Jian Shiyu, Huang Zhanpeng, Hou Yinchi, Qi Fang, Deng Chengliang
Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, PR China.
Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, PR China; The 2011 Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Affiliated Hospital of Zunyi Medical University, PR China; The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, PR China.
Int J Biol Macromol. 2025 Mar;297:139822. doi: 10.1016/j.ijbiomac.2025.139822. Epub 2025 Jan 12.
Chronic non-healing wounds are a common complication of diabetes, marked by impaired angiogenesis. This study explores how exosomes (Exo-miR-1248) from miR-1248-overexpressing adipose-derived stem cells enhance diabetic wound healing by modulating endothelial cell function. Adipose-derived stem cells were transfected with a lentivirus carrying miR-1248 to produce Exo-miR-1248, isolated via differential centrifugation. In vitro, Exo-miR-1248's effects on proliferation, scratch wound healing, and tube formation in human umbilical vein endothelial cells (HUVECs) were assessed. For in vivo analysis, diabetic mice were induced with streptozotocin (STZ) and full-thickness skin defects were created. The impact of Exo-miR-1248 on wound healing was evaluated through subcutaneous injections. Histological analysis included H&E staining for epithelial regeneration and wound width, Masson's staining for collagen deposition, immunofluorescence for CD31 and α-SMA expression, RT-qPCR and WB for mRNA and protein levels of pro-angiogenic genes (VEGF-A, TGF-β, and Angpt-1). Exo-miR-1248 significantly enhanced HUVEC proliferation and migration. Tube formation assays showed increased capillary-like structures. In vivo, Exo-miR-1248-treated wounds healed faster, with improved collagen deposition and blood vessel formation. RT-qPCR and WB show that the mRNA and protein levels of VEGF-A, Angpt-1, and TGF-β are upregulated. Exo-miR-1248 may enhance diabetic wound healing by upregulating pro-angiogenic factors, offering a novel therapeutic approach.
慢性难愈合伤口是糖尿病常见的并发症,其特征为血管生成受损。本研究探讨了来自过表达miR-1248的脂肪来源干细胞的外泌体(Exo-miR-1248)如何通过调节内皮细胞功能来促进糖尿病伤口愈合。用携带miR-1248的慢病毒转染脂肪来源干细胞以产生Exo-miR-1248,通过差速离心法分离。在体外,评估了Exo-miR-1248对人脐静脉内皮细胞(HUVECs)增殖、划痕伤口愈合和管腔形成的影响。对于体内分析,用链脲佐菌素(STZ)诱导糖尿病小鼠并制造全层皮肤缺损。通过皮下注射评估Exo-miR-1248对伤口愈合的影响。组织学分析包括用于上皮再生和伤口宽度的苏木精-伊红(H&E)染色、用于胶原沉积的Masson染色、用于CD31和α-SMA表达的免疫荧光、用于促血管生成基因(VEGF-A、TGF-β和Angpt-1)mRNA和蛋白质水平的逆转录-定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹(WB)。Exo-miR-1248显著增强了HUVEC的增殖和迁移。管腔形成试验显示毛细血管样结构增加。在体内,经Exo-miR-1248处理的伤口愈合更快,胶原沉积和血管形成得到改善。RT-qPCR和WB显示VEGF-A、Angpt-1和TGF-β的mRNA和蛋白质水平上调。Exo-miR-1248可能通过上调促血管生成因子来促进糖尿病伤口愈合,提供了一种新的治疗方法。