Renal Tubular Cell-Derived Extracellular Vesicles Accelerate the Recovery of Established Renal Ischemia Reperfusion Injury
Renal Tubular Cell-Derived Extracellular Vesicles Accelerate the Recovery of Established Renal Ischemia Reperfusion Injury
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DOI：
10.1681/asn.2016121278
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发表时间：
2017-12-01
影响因子：
13.6
通讯作者：
Kelly, K. J.
中科院分区：
文献类型：
--
作者：
Dominguez, Jesus H.;Liu, Yunlong;Kelly, K. J.
缺血性肾损伤是一种复杂的综合征;多种细胞异常导致炎症、细胞损伤和持续局部缺血的加速循环。没有一种单一的治疗方法可以有效地解决缺血后的肾损伤。然而，正常成年大鼠肾细胞的输注已在几种大鼠肾衰竭模型中成功治疗。通过相对较少的供体细胞实现的持续广泛的肾脏益处导致了这样的假设，即来源于这些细胞的细胞外囊泡（EV，主要是外来体）是原位治疗效应物。我们现在表明，EV从成年大鼠肾小管细胞显着改善肾功能时，静脉给药后24和48小时，大鼠肾缺血。此外，EV治疗显著改善了肾小管损伤、4-羟基纳米加合物形成、中性粒细胞浸润、纤维化和微血管修剪。EV治疗还显著减少了缺血后观察到的大的肾转录组漂移。这些数据显示了EV在发生后限制严重肾缺血性损伤的潜在效用。
Ischemic renal injury is a complex syndrome; multiple cellular abnormalities cause accelerating cycles of inflammation, cellular damage, and sustained local ischemia. There is no single therapy that effectively resolves the renal damage after ischemia. However, infusions of normal adult rat renal cells have been a successful therapy in several rat renal failure models. The sustained broad renal benefit achieved by relatively few donor cells led to the hypothesis that extracellular vesicles (EV, largely exosomes) derived from these cells are the therapeutic effector in situ. We now show that EV from adult rat renal tubular cells significantly improved renal function when administered intravenously 24 and 48 hours after renal ischemia in rats. Additionally, EV treatment significantly improved renal tubular damage, 4-hydroxynanoneal adduct formation, neutrophil infiltration, fibrosis, and microvascular pruning. EV therapy also markedly reduced the large renal transcriptome drift observed after ischemia. These data show the potential utility of EV to limit severe renal ischemic injury after the occurrence.