Erythropoietin-activated mesenchymal stem cells promote healing ulcers by improving microenvironment
Erythropoietin-activated mesenchymal stem cells promote healing ulcers by improving microenvironment
复制标题
促红细胞生成素激活的间充质干细胞通过改善微环境促进溃疡愈合。
DOI：
10.1016/j.jss.2016.06.086
复制
发表时间：
2016-10-01
影响因子：
2.2
通讯作者：
Zhu, Chuhong
中科院分区：
文献类型：
--
作者：
Lu, Hao;Wu, Xiaoyue;Zhu, Chuhong
背景：间充质干细胞（MSC）移植是治疗缺血性溃疡的有效方法。然而，在高糖微环境下，MSCs原有的炎症抑制功能导致其在糖尿病足溃疡愈合过程中大量分泌炎症介质，如肿瘤坏死因子α等，使其能力下降，成为质量较差的干细胞而不是炎症细胞，用于糖尿病足溃疡修复。促红细胞生成素（EPO）是一种抗炎、促血管生成的细胞因子。epo激活的MSCs与生物材料是否能促进糖尿病足溃疡的有效愈合尚不清楚。方法：用MSC-L、MSC-H、EPO-G、Akt-G、mTOR-G培养MSCs，分离各组上清培养基刺激人脐静脉内皮细胞增殖和迁移实验；将epo活化的MSCs植入一种新型生物材料，应用于C57小鼠糖尿病足溃疡。结果：体外实验显示EPO能刺激MSCs在高糖微环境下分泌血管内皮生长因子。更重要的是，EPO可以减轻高糖微环境对MSCs的损伤，促进其增殖和迁移功能，抑制高糖诱导的MSCs分泌炎症介质肿瘤坏死因子α。体内实验结果显示，EPO-MSC组血管生成明显大于对照组，溃疡愈合明显优于对照组，MSCs部分分化为内皮细胞。epo活化的MSCs可抑制局部糖尿病足溃疡单核细胞的侵袭。结论：epo活化的间充质干细胞能促进糖尿病足溃疡的有效愈合。其机制是EPO可将干细胞从过度炎症转变为一般炎症，改善糖尿病足溃疡炎症微环境。(C) 2016 Elsevier Inc.版权所有。
Background: Mesenchymal stem cell (MSC) transplantation is an effective treatment therapy for ischemic ulcers. However, in high-glucose microenvironment, the original inflammation-inhibiting function of MSCs leads to turns into secreting large amounts of inflammatory mediators, such as tumor necrosis factor alpha, for example, which decreases their capacity and becomes poor quality stem cells over inflammation cells for diabetic foot ulcers repair in the healing of diabetic foot ulcers. Erythropoietin (EPO) is an anti-inflammatory, proangiogenic cytokine. It is unclear whether EPO-activated MSCs with biomaterials can promote the effective healing of diabetic foot ulcers.Methods: Cultivated MSCs in MSC-L, MSC-H, EPO-G, Akt-G, and mTOR-G, then separated the supernatant-conditioned medium of these groups to stimulate human umbilical vein endothelial cells on proliferation and migration experiments; a new type of biomaterial planted with the EPO-activated MSCs was applied to the diabetic foot ulcers of the C57 mice.Results: In vitro experiments showed that EPO could stimulate MSCs to secrete vascular endothelial growth factor in high-glucose microenvironment. More importantly, EPO could reduce the damage to MSCs by high-glucose microenvironment, promote their proliferation and migration functions, and inhibit the high-glucose-induced MSCs from secreting the inflammatory mediator tumor necrosis factor alpha. In vivo experiments showed greater angiogenesis in EPO-MSC group than in control group, ulcer healing in EPO-MSC group was significantly better than that in control group, and MSCs partially differentiated into endothelial cells. EPO-activated MSCs could inhibit the monocyte invasion of localized diabetic foot ulcers.Conclusions: Our results indicate that EPO-activated MSCs can promote the effective healing of diabetic foot ulcers. The mechanism is that EPO can change stem cells from excessive inflammation into general inflammation and improved diabetic foot ulcers inflammatory microenvironment. (C) 2016 Elsevier Inc. All rights reserved.