Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No. 301 Middle Yan Chang Road, Shanghai, 200072, China.
Institute of Interventional & Vascular Surgery, Tongji University, No. 301 Middle Yan Chang Road, Shanghai, 200072, China.
Exp Mol Med. 2018 Apr 13;50(4):1-14. doi: 10.1038/s12276-018-0058-5.
Diabetic foot ulcers (DFU) increase the risks of infection and amputation in patients with diabetes mellitus (DM). The impaired function and senescence of endothelial progenitor cells (EPCs) and high glucose-induced ROS likely exacerbate DFUs. We assessed EPCs in 60 patients with DM in a hospital or primary care setting. We also evaluated the therapeutic effects of exosomes secreted from adipose-derived stem cells (ADSCs) on stress-mediated senescence of EPCs induced by high glucose. Additionally, the effects of exosomes and Nrf2 overexpression in ADSCs were investigated in vitro and in vivo in a diabetic rat model. We found that ADSCs that secreted exosomes promoted proliferation and angiopoiesis in EPCs in a high glucose environment and that overexpression of Nrf2 increased this protective effect. Wounds in the feet of diabetic rats had a significantly reduced ulcerated area when treated with exosomes from ADSCs overexpressing Nrf2. Increased granulation tissue formation, angiogenesis, and levels of growth factor expression as well as reduced levels of inflammation and oxidative stress-related proteins were detected in wound beds. Our data suggest that exosomes from ADSCs can potentially promote wound healing, particularly when overexpressing Nrf2 and therefore that the transplantation of exosomes may be suitable for clinical application in the treatment of DFUs.
糖尿病足溃疡（DFU）会增加糖尿病（DM）患者感染和截肢的风险。内皮祖细胞（EPCs）功能受损和衰老以及高血糖诱导的 ROS 可能会加重 DFU。我们在医院或初级保健机构评估了 60 名 DM 患者的 EPCs。我们还评估了脂肪来源干细胞（ADSCs）分泌的外泌体对高糖诱导的 EPC 应激介导衰老的治疗作用。此外，我们还在糖尿病大鼠模型中研究了外泌体和 ADSCs 中 Nrf2 过表达的体内和体外作用。我们发现，ADSCs 分泌的外泌体在高糖环境中促进 EPCs 的增殖和血管生成，而过表达 Nrf2 则增加了这种保护作用。用过表达 Nrf2 的 ADSC 的外泌体治疗糖尿病大鼠的足部伤口，溃疡面积明显减小。伤口床中检测到肉芽组织形成、血管生成和生长因子表达水平增加，以及炎症和氧化应激相关蛋白水平降低。我们的数据表明，ADSCs 的外泌体可能具有促进伤口愈合的潜力，特别是在过表达 Nrf2 的情况下，因此外泌体的移植可能适合用于 DFU 的临床治疗。
