Abstract
BackgroundDiabetic wounds threaten the health and quality of life of patients and their treatment remains challenging. ADSC-derived exosomes have shown encouraging results in enhancing diabetic wound healing. However, how to use exosomes in wound treatment effectively is a problem that needs to be addressed at present.MethodsA diabetic mouse skin wound model was established. ADSC-derived exosomes (ADSC-Exos) were isolated, and in vitro application of exosomes was evaluated using human umbilical vein endothelial cells (HUVECs) and human dermal fibroblasts (HDFs). After preparation and characterization of a scaffold of human acellular amniotic membrane (hAAM) loaded with ADSC-Exos in vitro, they were transplanted into wounds in vivo and wound healing phenomena were observed by histological and immunohistochemical analyses to identify the wound healing mechanism of the exosome-hAAM composites.ResultsThe hAAM scaffold dressing was very suitable for the delivery of exosomes. ADSC-Exos enhanced the proliferation and migration of HDFs and promoted proliferation and tube formation of HUVECs in vitro. In vivo results from a diabetic skin wound model showed that the hAAM-Exos dressing accelerated wound healing by regulating inflammation, stimulating vascularization, and promoting the production of extracellular matrix.ConclusionExosome-incorporated hAAM scaffolds showed great potential in promoting diabetic skin wound healing, while also providing strong evidence for the future clinical applications of ADSC-derived exosomes.
Highlights
With the high prevalence of diabetes around the world, complications such as diabetic wounds have become a serious threat to the health and quality of life of patients [1]
The matrix structures of native human amniotic membrane (hAM) and human acellular amniotic membrane (hAAM) were visualized by hematoxylin and eosin (H&E) staining and almost no residual cells were observed (Fig. 1a–d)
The results showed that adipose-derived mesenchymal stem cell (ADSC)-Exos promoted tube-forming ability of human umbilical vein endothelial cells (HUVECs) and migration of human dermal fibroblasts (HDFs) in a dose-dependent manner
Summary
With the high prevalence of diabetes around the world, complications such as diabetic wounds have become a serious threat to the health and quality of life of patients [1]. Mesenchymal stem cells (MSCs) have been demonstrated to be a promising new therapy for diabetic wound healing [6,7,8], yet many challenges remain, such as immunological rejection and chromosomal variation, as well as ethical issues, which limit their clinical utility [9, 10]. Emerging studies have shown that the beneficial effects of MSCs in vivo can be attributed to their paracrine action that regulates the functions of host cells and tissues [12,13,14]. Recent studies of the application of MSC-derived exosomes for promotion of healing of chronic diabetic wounds have shown encouraging results [17,18,19]. How to use exosomes in wound treatment effectively is a problem that needs to be addressed at present
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