The effectiveness of cell-derived exosome therapy for diabetic wound: A systematic review and meta-analysis

Background: The prevalence of diabetes among the elderly population is significant and rising annually. One of the most severe and frequent complications of diabetes mellitus is the diabetic wound, which has long-term negative effects on patients' finances, mental health, and functional abilities. Exosomes, a cell-free therapy, have emerged as a promising novel treatment for diabetic wounds, but their mechanism is still not entirely understood. Therefore, we conducted this meta-analysis to assess the effectiveness of exosomes in the management of diabetic wounds. Methods: We searched PubMed, the Cochrane Library, EMBASE, and Web of Science for pertinent studies that described the therapeutic benefits of exosomes on diabetic wound models that were released before October 17, 2022. The outcome indicators consisted of wound healing rate, neovascular density, re-epithelialization rate, collagen deposition, scar width, and inflammatory factors. RevMan 5.4 software was used to conduct all statistical analyses. Results: A total of 21 studies with 323 animals were identified in this meta-analysis. Pooled analyses demonstrated that exosome therapy was shown to be superior to control therapy in terms of wound healing rate (SMD = 5.42; 95 %CI = 4.40-6.44; P < 0.00001), neovascular density (SMD = 5.48; 95 %CI = 4.31-6.64; P < 0.00001), re-epithelialization rate (SMD = 5.06; 95 %CI = 3.75-6.37; P < 0.00001), collagen deposition (SMD = 4.78; 95 %CI = 3.58-5.98; P < 0.00001), scar width (SMD = -8.10; 95 %CI = -10.31 to -5.89; P < 0.00001). Additionally, the expression of inflammatory factors was significantly downregulated in the exosome treatment group. Conclusions: According to this meta-analysis of the current trials, exosome therapy can enhance the quality of diabetic wounds, especially when used in conjunction with novel dressings. To demonstrate the most efficient exosomes and therapeutic parameters for the treatment of diabetic wounds, future studies should conduct sizable, randomized, double-blind trials with high-quality, long-term follow-ups.