期刊
MOLECULAR PHARMACEUTICS
卷 17, 期 5, 页码 1723-1733出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.0c00177
关键词
engineered exosomes; adipose stem cells; miR-21; re-epithelialization; diabetic wound healing
资金
- National Natural Science Foundation of China [81572726, 51773231]
- Natural Science Foundation of Guangdong Pro vince [2014A030312018, 2016A030313315]
- Project of Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province [2011A060901013]
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.
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