School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, P. R. China.
Cardiovascular Division, Faculty of Life Science and Medicine, King's College London, SE5 9NU, UK.
Biomater Sci. 2024 Mar 26;12(7):1750-1760. doi: 10.1039/d3bm01904g.
Diabetes mellitus (DM) is characterized by prolonged hyperglycemia, impaired vascularization, and serious complications, such as blindness and chronic diabetic wounds. About 25% of patients with DM are estimated to encounter impaired healing of diabetic wounds, often leading to lower limb amputation. Multiple factors are attributed to the non-healing of diabetic wounds, including hyperglycaemia, chronic inflammation, and impaired angiogenesis. It is imperative to develop more efficient treatment strategies to tackle healing difficulties in diabetic wounds. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are promising for diabetic wound healing considering their anti-inflammatory, pro-angiogenic and pro-proliferative activities. A histone deacetylase 7 (HDAC7)-derived 7-amino-acid peptide (7A) was shown to be highly effective for angiogenesis. However, it has never been investigated whether MSC-EVs are synergistic with 7A for the healing of diabetic wounds. Herein, we propose that MSC-EVs can be combined with 7A to greatly promote diabetic wound healing. The combination of EVs and 7A significantly improved the migration and proliferation of skin fibroblasts. Moreover, EVs alone significantly suppressed LPS-induced inflammation in macrophages, and notably, the combination treatment showed an even better suppression effect. Importantly, the study revealed that the combination therapy consisting of EVs and 7A in an alginate hydrogel was more efficient for the healing of diabetic wounds in rats than monotherapy using either EV or 7A hydrogels. The underlying mechanisms include suppression of inflammation, improvement of skin cell proliferation and migration, and enhanced collagen fiber disposition and angiogenesis in wounds. In summary, the MSC-EV-7A hydrogel potentially constitutes a novel therapy for efficient healing of chronic diabetic wounds.
糖尿病（DM）的特征是长期高血糖、血管化受损以及严重的并发症，如失明和慢性糖尿病伤口。据估计，约 25%的糖尿病患者会遇到糖尿病伤口愈合受损的情况，这往往导致下肢截肢。多种因素导致糖尿病伤口无法愈合，包括高血糖、慢性炎症和血管生成受损。因此，迫切需要开发更有效的治疗策略来解决糖尿病伤口愈合的困难。鉴于间充质干细胞（MSC）衍生的细胞外囊泡（EVs）具有抗炎、促血管生成和促增殖作用，因此它们在糖尿病伤口愈合方面具有很大的应用前景。组蛋白去乙酰化酶 7（HDAC7）衍生的 7 个氨基酸肽（7A）已被证明对血管生成非常有效。然而，从未有人研究过 MSC-EVs 是否与 7A 协同作用促进糖尿病伤口愈合。在此，我们提出 MSC-EVs 可以与 7A 联合使用，极大地促进糖尿病伤口愈合。EVs 和 7A 的联合使用显著促进了皮肤成纤维细胞的迁移和增殖。此外，EVs 单独使用可显著抑制 LPS 诱导的巨噬细胞炎症，值得注意的是，联合治疗显示出更好的抑制效果。重要的是，该研究表明，EVs 和 7A 的联合治疗在促进糖尿病大鼠伤口愈合方面比单独使用 EV 或 7A 水凝胶的单一疗法更有效。其潜在机制包括抑制炎症、改善皮肤细胞增殖和迁移以及增强伤口中胶原纤维的排列和血管生成。总之，MSC-EV-7A 水凝胶可能为慢性糖尿病伤口的高效愈合提供一种新的治疗方法。
