Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model
Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model
复制标题
骨髓干细胞衍生的微泡可防止小鼠残肾模型中的肾损伤
DOI：
10.1111/j.1440-1797.2012.01589.x
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发表时间：
2012-07-01
期刊：
影响因子：
2.5
通讯作者：
Zhao, Weihong
中科院分区：
文献类型：
--
作者：
He, Juan;Wang, Yan;Zhao, Weihong
目的：几项研究表明，间充质干细胞（MSC）的管理可以逆转肾损伤的旁分泌机制，而不是MSC转分化。最近，一些研究者发现来源于MSC的微泡（MV）可能是细胞间通讯的一种旁分泌机制。本研究的目的是研究MV在5/6肾大部切除（Nx）小鼠模型中的修复作用。方法：动物随机分为对照组、Nx组、Nx + MSC组和Nx + MV组。在手术后第二天，在Nx + MSC组中通过尾静脉注射MSC（1 × 106/小鼠），并且在Nx + MV组中通过尾静脉隔天注射MV（30 μ g/小鼠）。在第一次给药后第7天处死小鼠。检测血尿素氮（BUN）、血肌酐（Scr）、尿酸（UA）、尿蛋白。并进行肾脏组织学分析。结果：MV和MSC均能显著降低Nx小鼠的血肌酐、尿酸和尿蛋白水平（P < 0.05）。MV和MSC处理的Nx小鼠的残肾显示出较少的纤维化，间质淋巴细胞浸润和较少或不存在肾小管萎缩与未处理的Nx组相比。未治疗小鼠的肾脏组织学评分为3.13 +/- 0.74，而MSC治疗组为1.67 +/- 0.47，MV治疗组为1.80 +/- 0.44，几乎保持了正常的肾脏形态（P < 0.01）。结论：MV对5/6 Nx诱导的肾损伤具有保护作用，可模拟MSC的肾修复作用。这项研究为肾脏疾病提供了一种新的潜在治疗方法。
Aims: Several studies have demonstrated administration of mesenchymal stem cells (MSC) could reverse kidney injury by paracrine mechanisms rather than by MSC transdifferentiation. Recently, a few researchers found microvesicles (MV) derived from MSC might be a paracrine mechanism for cell-to-cell communication. The aim of this study was to investigate the repair effects of MV in a 5/6 subtotal nephrectomy (Nx) mice model. Methods: The animals were randomly divided into four groups: Control, Nx, Nx + MSC and Nx + MV group. MSC were injected (1 x 106/mouse) through caudal vein in Nx + MSC group at the second day after the surgery and MV were injected (30 mu g/mouse) through caudal vein in Nx + MV group on alternate days. Mice were killed on day 7 after the first time of administration. Blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA) and proteinuria were evaluated. Histopathology of kidney was analysed. Results: In Nx mice, the levels of Scr, UA and proteinuria were significantly decreased with administration of MV and MSC (P < 0.05). The remnant kidneys of MV and MSC-treated Nx mice showed less fibrosis, interstitial lymphocyte infiltrates and less or absent tubular atrophy compared with the untreated Nx group. The Histological Score of Kidney in untreated mice was 3.13 +/- 0.74, while in the MSC-treated group it was 1.67 +/- 0.47 and in the MV-treated group it was 1.80 +/- 0.44, nearly preserving normal morphology of the kidney (P < 0.01). Conclusion: This study showed MV protects against renal injury induced by 5/6 Nx, which could mimic the role of MSC in kidney repair. The research showed a newly potential therapeutic approach to kidney diseases.