Department of Urology, Henan Provincial People's Hospital, Zhengzhou, China.
J Cell Biochem. 2018 Feb;119(2):1879-1888. doi: 10.1002/jcb.26348. Epub 2017 Sep 7.
The purpose of the present study was to investigate the possible therapeutic effects of the human Wharton-Jelly mesenchymal stromal cells derived micro-vesicles (hWJMSCs-MVs) on renal ischemia-reperfusion injury (IRI) after cardiac death (CD) renal transplantation in rats. MVs were injected intravenously in rats immediately after renal transplantation. The animals were sacrificed at 24 h, 48 h, 1 and 2 weeks post-transplantation. ELISA was used to determine the von Willebrand Factor (vWF), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 levels in the serum. Tubular cell proliferation and apoptosis were identified by Ki67 immunostaining and TUNEL assay. Renal fibrosis was assessed by Masson's tri-chrome straining and alpha-smooth muscle actin (α-SMA) staining. The infiltration of inflammatory cells was detected by CD68 staining. The transforming growth factor (TGF)-β, hepatocyte growth factor (HGF), and α-SMA expression in the kidney was measured by Western blot. After renal transplantation, the rats treated with hWJMSCs-MVs improved survival rate and renal function. Moreover, MVs mitigated renal cell apoptosis, enhanced proliferation, and alleviated inflammation at the first 48 h. In the late period, abrogation of renal fibrosis was observed in the MVs group. MVs also could decrease the number of CD68 macrophages in the kidney. Furthermore, MVs decreased the protein expression levels of α-SMA and TGF-β1 and increased the protein expression level of HGF at any point (24 h, 48 h, 1 or 2 weeks). The administration of MVs immediately after renal transplantation could ameliorate IRI in both the acute and chronic stage.
本研究旨在探讨人脐带 Wharton Jelly 间充质基质细胞衍生的微囊泡（hWJMSCs-MVs）对心脏死亡（CD）肾移植后大鼠肾缺血再灌注损伤（IRI）的可能治疗作用。MVs 在肾移植后立即静脉注射到大鼠体内。动物在移植后 24、48、1 和 2 周时处死。ELISA 法测定血清中血管性血友病因子（vWF）、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-10水平。Ki67 免疫组化和 TUNEL 检测肾小管细胞增殖和凋亡。Masson 三色染色和α-平滑肌肌动蛋白（α-SMA）染色评估肾纤维化。CD68 染色检测炎性细胞浸润。Western blot 检测肾组织中转化生长因子（TGF）-β、肝细胞生长因子（HGF）和α-SMA 的表达。肾移植后，hWJMSCs-MVs 治疗组提高了大鼠的存活率和肾功能。此外，MVs 在最初 48 小时内减轻了肾小管细胞凋亡，促进了增殖，减轻了炎症。在后期，MVs 组观察到肾纤维化减轻。MVs 还可以减少肾组织中 CD68 巨噬细胞的数量。此外，MVs 在任何时间点（24、48、1 或 2 周）均降低了α-SMA 和 TGF-β1 的蛋白表达水平，增加了 HGF 的蛋白表达水平。MVs 在肾移植后立即给药可改善急性和慢性阶段的 IRI。
