Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Institute of Stem Cell, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
Cell Cycle. 2021 Mar-Mar;20(5-6):616-629. doi: 10.1080/15384101.2021.1894813. Epub 2021 Mar 8.
Diabetic cutaneous wounds are one of the complications of diabetes mellitus (DM) and are difficult to cure at present. Autologous dermal fibroblasts (DFs) have shown great promise in skin regeneration and repair. However, whether exosomes derived from autologous dermal fibroblasts (DF-Ex) can be used to accelerate diabetic cutaneous wound healing is unclear. In this study, human umbilical vein endothelial cells (HUVECs) were treated with high glucose. We found that DF-Ex could reverse the damage produced by high glucose in HUVECs in vitro. A high-fat diet and streptozotocin were used to establish a rat model of type 2 diabetes mellitus (T2DM), and a diabetic cutaneous wound model was established in the T2DM rats. We discovered that subcutaneous injections of DF-Ex could significantly promote re-epithelialization, collagen deposition, skin cell proliferation, angiogenesis and inhibit inflammation to accelerate diabetic cutaneous wound healing. We further explored the underlying mechanism and found that DF-Ex exerted positive effects by activating the Akt/β-catenin pathway. This research revealed that DF-Ex may provide a new treatment strategy for diabetic cutaneous wound healing.
糖尿病性皮肤创面是糖尿病（DM）的并发症之一，目前难以治愈。自体真皮成纤维细胞（DF）在皮肤再生和修复方面显示出巨大的潜力。然而，自体真皮成纤维细胞来源的外泌体（DF-Ex）是否可用于加速糖尿病性皮肤创面愈合尚不清楚。本研究中，用人脐带静脉内皮细胞（HUVEC）处理高葡萄糖。我们发现，DF-Ex 可以逆转体外高葡萄糖对 HUVEC 产生的损伤。采用高脂饮食和链脲佐菌素建立 2 型糖尿病（T2DM）大鼠模型，并在 T2DM 大鼠中建立糖尿病性皮肤创面模型。我们发现，DF-Ex 皮下注射可显著促进再上皮化、胶原沉积、皮肤细胞增殖、血管生成，并抑制炎症反应，从而加速糖尿病性皮肤创面愈合。我们进一步探讨了其潜在机制，发现 DF-Ex 通过激活 Akt/β-catenin 通路发挥积极作用。该研究揭示了 DF-Ex 可能为糖尿病性皮肤创面愈合提供新的治疗策略。
