Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model.
Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model.
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来自过度表达 Nrf2 的脂肪干细胞的外泌体通过促进糖尿病足溃疡大鼠模型中的血管形成来加速皮肤伤口愈合
DOI：
10.1038/s12276-018-0058-5
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发表时间：
2018-04-13
影响因子：
12.8
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Li X;Xie X;Lian W;Shi R;Han S;Zhang H;Lu L;Li M
糖尿病足溃疡（DFU）增加了糖尿病（DM）患者感染和截肢的风险。内皮祖细胞（EPCs）的功能受损和衰老以及高糖诱导的ROS可能会加剧DFU。我们评估了60例糖尿病患者的内皮祖细胞在医院或初级保健设置。我们还评估了脂肪干细胞（ADSC）分泌的外泌体对高糖诱导的EPCs应激介导的衰老的治疗作用。此外，在体外和体内在糖尿病大鼠模型中研究了ADSC中外泌体和Nrf2过表达的作用。我们发现，在高糖环境下，分泌外泌体的ADSC促进了EPCs的增殖和血管生成，Nrf2的过表达增强了这种保护作用。当用来自过表达Nrf2的ADSC的外泌体治疗时，糖尿病大鼠足部的伤口具有显著减少的溃疡面积。在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，来自ADSC的外泌体可以潜在地促进伤口愈合，特别是当过表达Nrf2时，因此外泌体的移植可能适用于治疗DFU的临床应用。
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.
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影响因子：
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作者：
Kota SK;Meher LK;Jammula S;Kota SK;Krishna SV;Modi KD
通讯作者：
Modi KD
影响因子：
3.7
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Meng S;Cao J;Zhang X;Fan Y;Fang L;Wang C;Lv Z;Fu D;Li Y
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Chilukuri N
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Ruszkowska-Ciastek, Barbara;Sokup, Alina;Rosc, Danuta
通讯作者：
Rosc, Danuta
影响因子：
11
作者：
Suthar M;Gupta S;Bukhari S;Ponemone V
通讯作者：
Ponemone V