Engineered Human Adipose Stem Cell-derived Exosomes Loaded with miR-21-5p to Promote Diabetic Cutaneous Wound Healing.

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/beta-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.