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GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

Background: Delayed wound healing in diabetic patients is one of the most challenging complications in clinical medicine, as it poses a greater risk of gangrene, amputation and even death. Therefore, a novel method to promote diabetic wound healing is of considerable interest at present. Previous st...

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Detalles Bibliográficos
Autores principales: Shi, Quan, Qian, Zhiyong, Liu, Donghua, Sun, Jie, Wang, Xing, Liu, Hongchen, Xu, Juan, Guo, Ximin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681946/
https://www.ncbi.nlm.nih.gov/pubmed/29163228
http://dx.doi.org/10.3389/fphys.2017.00904
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author Shi, Quan
Qian, Zhiyong
Liu, Donghua
Sun, Jie
Wang, Xing
Liu, Hongchen
Xu, Juan
Guo, Ximin
author_facet Shi, Quan
Qian, Zhiyong
Liu, Donghua
Sun, Jie
Wang, Xing
Liu, Hongchen
Xu, Juan
Guo, Ximin
author_sort Shi, Quan
collection PubMed
description Background: Delayed wound healing in diabetic patients is one of the most challenging complications in clinical medicine, as it poses a greater risk of gangrene, amputation and even death. Therefore, a novel method to promote diabetic wound healing is of considerable interest at present. Previous studies showed that injection of MSC-derived exosomes has beneficial effects on wound healing. In current studies, we aimed to isolate exosomes derived from gingival mesenchymal stem cells (GMSCs) and then loading them to the chitosan/silk hydrogel sponge to evaluate the effects of this novel non-invasive method on skin defects in diabetic rats. Methods: GMSCs were isolated from human gingival connective tissue and characterized by surface antigen analysis and in vitro multipotent differentiation. The cell supernatant was collected to isolate the exosomes. The exosomes were characterized by transmission electron microscopy, Western blot and size distribution analysis. The chitosan/silk-based hydrogel sponge was prepared using the freeze-drying method and then structural and physical properties were characterized. Then, the exosomes were added to the hydrogel and tested in a diabetic rat skin defect model. The effects were evaluated by wound area measurement, histological, immunohistochemical and immunofluorescence analysis. Results: We have successfully isolated GMSCs and exosomes with a mean diameter of 127 nm. The chitosan/silk hydrogel had the appropriate properties of swelling and moisture retention capacity. The in vivo studies showed that the incorporating of GMSC-derived exosomes to hydrogel could effectively promote healing of diabetic skin defects. The histological analysis revealed more neo-epithelium and collagen in the hydrogel-exosome group. In addition, the hydrogel-exosome group had the highest microvessel density and nerve density. Conclusions: The combination of GMSC-derived exosomes and hydrogel could effectively promote skin wound healing in diabetic rats by promoting the re-epithelialization, deposition and remodeling of collagen and by enhancing angiogenesis and neuronal ingrowth. These findings not only provide new information on the role of the GMSC-derived exosomes in wound healing but also provide a novel non-invasive application method of exosomes with practical value for skin repair.
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spelling pubmed-56819462017-11-21 GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model Shi, Quan Qian, Zhiyong Liu, Donghua Sun, Jie Wang, Xing Liu, Hongchen Xu, Juan Guo, Ximin Front Physiol Physiology Background: Delayed wound healing in diabetic patients is one of the most challenging complications in clinical medicine, as it poses a greater risk of gangrene, amputation and even death. Therefore, a novel method to promote diabetic wound healing is of considerable interest at present. Previous studies showed that injection of MSC-derived exosomes has beneficial effects on wound healing. In current studies, we aimed to isolate exosomes derived from gingival mesenchymal stem cells (GMSCs) and then loading them to the chitosan/silk hydrogel sponge to evaluate the effects of this novel non-invasive method on skin defects in diabetic rats. Methods: GMSCs were isolated from human gingival connective tissue and characterized by surface antigen analysis and in vitro multipotent differentiation. The cell supernatant was collected to isolate the exosomes. The exosomes were characterized by transmission electron microscopy, Western blot and size distribution analysis. The chitosan/silk-based hydrogel sponge was prepared using the freeze-drying method and then structural and physical properties were characterized. Then, the exosomes were added to the hydrogel and tested in a diabetic rat skin defect model. The effects were evaluated by wound area measurement, histological, immunohistochemical and immunofluorescence analysis. Results: We have successfully isolated GMSCs and exosomes with a mean diameter of 127 nm. The chitosan/silk hydrogel had the appropriate properties of swelling and moisture retention capacity. The in vivo studies showed that the incorporating of GMSC-derived exosomes to hydrogel could effectively promote healing of diabetic skin defects. The histological analysis revealed more neo-epithelium and collagen in the hydrogel-exosome group. In addition, the hydrogel-exosome group had the highest microvessel density and nerve density. Conclusions: The combination of GMSC-derived exosomes and hydrogel could effectively promote skin wound healing in diabetic rats by promoting the re-epithelialization, deposition and remodeling of collagen and by enhancing angiogenesis and neuronal ingrowth. These findings not only provide new information on the role of the GMSC-derived exosomes in wound healing but also provide a novel non-invasive application method of exosomes with practical value for skin repair. Frontiers Media S.A. 2017-11-07 /pmc/articles/PMC5681946/ /pubmed/29163228 http://dx.doi.org/10.3389/fphys.2017.00904 Text en Copyright © 2017 Shi, Qian, Liu, Sun, Wang, Liu, Xu and Guo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Shi, Quan
Qian, Zhiyong
Liu, Donghua
Sun, Jie
Wang, Xing
Liu, Hongchen
Xu, Juan
Guo, Ximin
GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model
title GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model
title_full GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model
title_fullStr GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model
title_full_unstemmed GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model
title_short GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model
title_sort gmsc-derived exosomes combined with a chitosan/silk hydrogel sponge accelerates wound healing in a diabetic rat skin defect model
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681946/
https://www.ncbi.nlm.nih.gov/pubmed/29163228
http://dx.doi.org/10.3389/fphys.2017.00904
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