GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model.
GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model.
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DOI：
10.3389/fphys.2017.00904
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发表时间：
2017
影响因子：
4
通讯作者：
Guo X
中科院分区：
文献类型：
--
作者：
Shi Q;Qian Z;Liu D;Sun J;Wang X;Liu H;Xu J;Guo X
背景：糖尿病患者的伤口愈合延迟是临床医学中最具挑战性的并发症之一，因为它会带来更大的坏疽、截肢甚至死亡的风险。因此，目前促进糖尿病伤口愈合的新方法引起了人们的极大兴趣。先前的研究表明，注射间充质干细胞衍生的外泌体对伤口愈合具有有益作用。在目前的研究中，我们的目的是分离源自牙龈间充质干细胞（GMSC）的外泌体，然后将其加载到壳聚糖/丝水凝胶海绵中，以评估这种新型非侵入性方法对糖尿病大鼠皮肤缺损的影响。方法：从人牙龈结缔组织中分离GMSC，并通过表面抗原分析和体外多能分化进行表征。收集细胞上清液以分离外泌体。通过透射电子显微镜、蛋白质印迹和大小分布分析来表征外泌体。采用冷冻干燥方法制备了壳聚糖/丝基水凝胶海绵，并对其结构和物理性能进行了表征。然后，将外泌体添加到水凝胶中并在糖尿病大鼠皮肤缺损模型中进行测试。通过伤口面积测量、组织学、免疫组织化学和免疫荧光分析来评估效果。结果：我们成功分离出平均直径为127 nm的GMSC和外泌体。壳聚糖/丝水凝胶具有适当的溶胀和保湿能力。体内研究表明，将 GMSC 衍生的外泌体掺入水凝胶中可以有效促进糖尿病皮肤缺损的愈合。组织学分析显示水凝胶-外泌体组中有更多的新上皮和胶原蛋白。此外，水凝胶-外泌体组的微血管密度和神经密度最高。结论：GMSC来源的外泌体和水凝胶的组合可以通过促进胶原蛋白的再上皮化、沉积和重塑以及增强血管生成和神经元向内生长来有效促进糖尿病大鼠皮肤伤口愈合。这些发现不仅为GMSC来源的外泌体在伤口愈合中的作用提供了新的信息，而且为皮肤修复提供了一种新型的非侵入性应用外泌体方法，具有实用价值。
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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影响因子：
4.3
作者：
Fawzy El-Sayed KM;Dörfer CE
通讯作者：
Dörfer CE
影响因子：
5.7
作者：
Dai T;Tanaka M;Huang YY;Hamblin MR
通讯作者：
Hamblin MR
影响因子：
--
作者：
Berlanga-Acosta J;Schultz GS;López-Mola E;Guillen-Nieto G;García-Siverio M;Herrera-Martínez L
通讯作者：
Herrera-Martínez L
影响因子：
3.5
作者：
Jin, S. H.;Lee, J. E.;Park, J. B.
通讯作者：
Park, J. B.
影响因子：
4.1
作者：
Moshaverinia, Alireza;Chen, Chider;Shi, Songtao
通讯作者：
Shi, Songtao