Diabetic wounds are a worldwide health problem causing extremely heavy public health burden and require effective treatment. Optimal strategies for treating nonhealing diabetic wounds include stem-cell-based therapy and delivery of novel drug substances, such as functional microRNAs (miRNAs); however, miRNA easily degrades in the wound microenvironment. Herein, we developed a human adipose stem-cell-derived exosome (hASC-exos)-based miRNA delivery strategy to enhance its therapeutic efficacy. The miR-21-5p mimics, as novel therapeutic candidates for diabetic wounds, were loaded into hASC-exos by electroporation, taking advantage of natural availability and biocompatibility of exosomes as extracellular miRNA transporting particles. The engineered exosomes (E-exos) exhibited excellent effects on promoting proliferation and migration of keratinocytes via Wnt/β-catenin signaling in vitro and accelerating diabetic wound healing by increasing re-epithelialization, collagen remodeling, angiogenesis, and vessel maturation in vivo. Results from this study would set the fundamentals of applying hASC-exos to deliver future drug substances and to develop cell-free therapy for wound-healing treatments.

中文翻译：

---

工程化人类脂肪干细胞衍生的外泌体负载 miR-21-5p，以促进糖尿病皮肤伤口愈合。

糖尿病伤口是一个世界性的健康问题，会造成极其沉重的公共卫生负担，需要有效的治疗。治疗不愈合糖尿病伤口的最佳策略包括基于干细胞的治疗和新药物的递送，例如功能性 microRNA (miRNA)；然而，miRNA 很容易在伤口微环境中降解。在此，我们开发了一种基于人类脂肪干细胞衍生的外泌体 (hASC-exos) 的 miRNA 递送策略，以提高其治疗效果。miR-21-5p 模拟物，作为糖尿病伤口的新型治疗候选物，通过电穿孔加载到 hASC-exos 中，利用外泌体作为细胞外 miRNA 转运颗粒的自然可用性和生物相容性。工程化外泌体（E-exos）在体外通过 Wnt/β-catenin 信号传导促进角质形成细胞的增殖和迁移，并通过增加体内上皮再形成、胶原重塑、血管生成和血管成熟来加速糖尿病伤口愈合。这项研究的结果将为应用 hASC-exos 提供未来的药物物质和开发用于伤口愈合治疗的无细胞疗法奠定基础。