title: Chitosan Wound Dressings Incorporating Exosomes Derived from MicroRNA-126-Overexpressing Synovium Mesenchymal Stem Cells Provide Sustained Release of Exosomes and Heal Full-Thickness Skin Defects in a Diabetic Rat Model.
abstract: There is a need to find better strategies to promote wound healing, especially of chronic wounds, which remain a challenge. We found that synovium mesenchymal stem cells (SMSCs) have the ability to strongly promote cell proliferation of fibroblasts; however, they are ineffective at promoting angiogenesis. Using gene overexpression technology, we overexpressed microRNA-126-3p (miR-126-3p) and transferred the angiogenic ability of endothelial progenitor cells to SMSCs, promoting angiogenesis. We tested a therapeutic strategy involving controlled-release exosomes derived from miR-126-3p-overexpressing SMSCs combined with chitosan. Our in vitro results showed that exosomes derived from miR-126-3p-overexpressing SMSCs (SMSC-126-Exos) stimulated the proliferation of human dermal fibroblasts and human dermal microvascular endothelial cells (HMEC-1) in a dose-dependent manner. Furthermore, SMSC-126-Exos also promoted migration and tube formation of HMEC-1. Testing this system in a diabetic rat model, we found that this approach resulted in accelerated re-epithelialization, activated angiogenesis, and promotion of collagen maturity in vivo. These data provide the first evidence of the potential of SMSC-126-Exos in treating cutaneous wounds and indicate that modifying the cells-for example, by gene overexpression-and using the exosomes derived from these modified cells provides a potential drug delivery system and could have infinite possibilities for future therapy. Stem Cells Translational Medicine 2017;6:736-747.
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Shi-Cong
authors.initials: SC
authors.lastname: Tao
authors.affiliation: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Shang-Chun
authors.initials: SC
authors.lastname: Guo
authors.affiliation: The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai, People's Republic of China.
authors.forename: Qin-Fei
authors.initials: QF
authors.lastname: Ke
authors.affiliation: The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai, People's Republic of China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Guo
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.|Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001458:Bandages; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D055354:Exosomes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D013583:Synovial Membrane / Q000166:cytology*; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D003692:Delayed-Action Preparations; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D048271:Chitosan
keywords: Angiogenesis; Control release; Exosomes; Gene modification; Synovium mesenchymal stem cells; Wound healing