Human umbilical cord mesenchymal stem cells attenuate cisplatin-induced acute and chronic renal injury

Human umbilical cord mesenchymal stem cells attenuate cisplatin-induced acute and chronic renal injury
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人脐带间充质干细胞减轻顺铂引起的急慢性肾损伤

DOI:
10.1177/1535370213497176
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发表时间:
2013-08-01
影响因子:
3.2
通讯作者:
Qian, Hui
Qian, Hui
中科院分区:
医学4区
文献类型:
--
作者:
Peng, Xiujuan;Xu, Huitao;Qian, Hui

文献摘要

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间充质干细胞正在成为治疗急性肾损伤(AKI)的有前途的候选细胞。我们首次报道了人脐带间充质干细胞(HucMSCs)可以改善缺血再灌注AKI大鼠的肾功能,但hucMSCs在顺铂诱导的急、慢性肾损伤中的作用已被证实。更具体地说,目前还不清楚hucMSCs是否能阻止肾间质纤维化。本研究观察hucMSCs在顺铂诱导的肾损伤中的作用,并探讨其作用机制。血尿素氮(BUN)和肌酐(Cr)分析显示,hucMSC治疗的大鼠在损伤早期功能参数有所改善。HucMSCs移植可促进肾细胞再生,抑制细胞凋亡,消除炎症反应,保护线粒体。此外,Masson‘s三色染色显示,在注射顺铂后6周和8周,hucMSC处理的大鼠肾组织纤维化水平降低。胶原沉积减少、Bax/Bcl2比值和转化生长因子βmRNA的表达均证实了上述结果。此外,hucMSCs阻止了损伤肾组织的上皮-间充质转化(EMT),导致慢性肾间质纤维化的减轻。综上所述,我们的研究结果提示hucMSCs可以通过改善早期AKI来减少晚期肾间质纤维化的发生。
Mesenchymal stem cell is becoming a promising candidate in acute kidney injury (AKI). We first reported that human umbilical cord mesenchymal stem cells (hucMSCs) could ameliorate renal function in ischemic/reperfusion AKI rats, but the role of hucMSCs in cisplatin-induced acute and chronic injury has been demonstrated. More specifically, it is still unknown whether hucMSCs halt renal interstitial fibrosis. In this study, we investigated the effect of hucMSCs in cisplatin-induced kidney injury and explored the mechanism of action. Blood urea nitrogen (BUN) and creatinine (Cr) analyses showed amelioration of functional parameters in hucMSC-treated rats at early damage. Transplantation with hucMSCs promoted renal cell regeneration, inhibited cell apoptosis, abrogated inflammatory responses and protected mitochondria. Moreover, Masson's trichrome staining demonstrated reduced levels of fibrosis in kidney tissues of hucMSC-treated rats at six and eight weeks after cisplatin injection. These results were corroborated by reduced collagen deposit, the ratio of Bax to Bcl-2 and transforming growth factor beta mRNA expression. Furthermore, hucMSCs prevented the epithelial-mesenchymal transition (EMT) in injury renal tissues, leading to the attenuation of chronic renal interstitial fibrosis. Taken together, our findings suggested that hucMSCs could decrease the kidney from development of later renal interstitial fibrosis by amelioration of early AKI.