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

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          Abstract

          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.

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          Author and article information

          Journal
          Mol. Pharm.
          Molecular pharmaceutics
          American Chemical Society (ACS)
          1543-8392
          1543-8384
          May 04 2020
          : 17
          : 5
          Affiliations
          [1 ] Department of General Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510120, China.
          [2 ] School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
          Article
          10.1021/acs.molpharmaceut.0c00177
          32233440
          d4ccd287-2588-4b86-a325-c4cd7ca44b1b
          History

          re-epithelialization,miR-21,engineered exosomes,diabetic wound healing,adipose stem cells

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