Chronic wounds including diabetic foot ulcers are clinical emergencies that need careful management. Exosomes from human adipose-derived mesenchymal stem cells (hADSCs-Ex) are a new promising cell-free therapy for the regeneration of dermal wounds. We established a delayed wound healing model using diabetic female mice. A 1.5 cm² full-thickness cutaneous wound was made ventrally in 6-week-old db/db mice. After treatment with phosphate-buffered saline, recombinant human epidermal growth factor, hADSCs-CM, or hADSCs-Ex three times a day for 2 weeks, we measured wound healing closure rates and performed histological analysis. Human dermal fibroblasts (WS1) were evaluated by PKH26-Exo co-localization test, CCK-8 test, cell scratch test, and the transwell test, while the expression of matrix metalloproteinase-1 (MMP1), MMP3, Collagen I, and Collagen III were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Wound closure and re-epithelialization were accelerated by hADSCs-Ex. Besides, hADSCs-Ex enhanced skin collagen production, angiogenesis, cell proliferation, inhibited apoptosis, promoted skin barrier function repair, and reduced inflammation in skin lesions. Furthermore, negative regulation of MMP1 and MMP3 enhanced collagen synthesis wound healing-promoting effects of hADSCs-Ex. hADSCs-Ex treatment for diabetic wounds provided a novel cell-free therapeutic strategy.

中文翻译：

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人类外泌体通过促进糖尿病小鼠模型中的胶原合成来加速皮肤伤口愈合

包括糖尿病足溃疡在内的慢性伤口是临床急症，需要小心处理。来自人类脂肪间充质干细胞 (hADSCs-Ex) 的外泌体是一种新的有前途的无细胞疗法，可用于皮肤伤口的再生。我们使用糖尿病雌性小鼠建立了延迟伤口愈合模型。一个 1.5 厘米²在 6 周龄 db/db 小鼠的腹侧进行全层皮肤伤口。在用磷酸盐缓冲盐水、重组人表皮生长因子、hADSCs-CM 或 hADSCs-Ex 治疗后，每天 3 次，持续 2 周，我们测量了伤口愈合闭合率并进行了组织学分析。通过PKH26-Exo共定位试验、CCK-8试验、细胞划痕试验和transwell试验评估人真皮成纤维细胞（WS1），而基质金属蛋白酶1（MMP1）、MMP3、胶原蛋白I和胶原蛋白的表达III通过定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹分析。hADSCs-Ex 加速了伤口闭合和再上皮化。此外，hADSCs-Ex 增强皮肤胶原蛋白生成、血管生成、细胞增殖、抑制细胞凋亡、促进皮肤屏障功能修复、并减少皮肤损伤的炎症。此外，MMP1 和 MMP3 的负调控增强了 hADSCs-Ex 的胶原合成促进伤口愈合的作用。hADSCs-Ex 治疗糖尿病伤口提供了一种新的无细胞治疗策略。