Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury.
Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury.
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DOI：
10.1371/journal.pone.0033115
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Camussi G
中科院分区：
文献类型：
--
作者：
Bruno S;Grange C;Collino F;Deregibus MC;Cantaluppi V;Biancone L;Tetta C;Camussi G
几项研究表明，用间充质干细胞（MSC）治疗可降低顺铂在小鼠中的死亡率。从MSC释放的微囊泡（MV）先前被证明有利于非致死性毒性和缺血性急性肾损伤（阿基）的肾修复。在本研究中，我们研究了MSC衍生的MV在致死性顺铂诱导的阿基中对SCID小鼠存活的影响。此外，我们在体外评估了MVs对顺铂诱导的人肾小管上皮细胞凋亡的影响及其分子机制。采用两种不同的MV注射方案。单次给予MV可改善肾功能和形态，并提高生存率，但不能预防慢性肾小管损伤和BUN和肌酐持续升高。多次注射MV进一步降低了死亡率，在第21天，存活小鼠显示出正常的组织学和肾功能。其保护机制主要是通过抗凋亡作用实现的。体外研究表明，在顺铂处理的人肾小管上皮细胞中，MV上调了抗凋亡基因，如Bcl-xL、Bcl 2和BIRC 8，下调了在细胞凋亡执行阶段具有核心作用的基因，如Casp 1、Casp 8和LTA。总之，发现从MSC释放的MV在体外和体内对肾细胞发挥促存活作用，表明MV可能有助于MSC赋予的肾保护。
Several studies demonstrated that treatment with mesenchymal stem cells (MSCs) reduces cisplatin mortality in mice. Microvesicles (MVs) released from MSCs were previously shown to favor renal repair in non lethal toxic and ischemic acute renal injury (AKI). In the present study we investigated the effects of MSC-derived MVs in SCID mice survival in lethal cisplatin-induced AKI. Moreover, we evaluated in vitro the effect of MVs on cisplatin-induced apoptosis of human renal tubular epithelial cells and the molecular mechanisms involved. Two different regimens of MV injection were used. The single administration of MVs ameliorated renal function and morphology, and improved survival but did not prevent chronic tubular injury and persistent increase in BUN and creatinine. Multiple injections of MVs further decreased mortality and at day 21 surviving mice showed normal histology and renal function. The mechanism of protection was mainly ascribed to an anti-apoptotic effect of MVs. In vitro studies demonstrated that MVs up-regulated in cisplatin-treated human tubular epithelial cells anti-apoptotic genes, such as Bcl-xL, Bcl2 and BIRC8 and down-regulated genes that have a central role in the execution-phase of cell apoptosis such as Casp1, Casp8 and LTA. In conclusion, MVs released from MSCs were found to exert a pro-survival effect on renal cells in vitro and in vivo, suggesting that MVs may contribute to renal protection conferred by MSCs.
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影响因子：
3.7
作者：
Collino F;Deregibus MC;Bruno S;Sterpone L;Aghemo G;Viltono L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
6.1
作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
3.7
作者：
Collino, Federica;Revelli, Alberto;Bussolati, Benedetta
通讯作者：
Bussolati, Benedetta
影响因子：
23.9
作者：
Humphreys, Benjamin D.;Valerius, M. Todd;Bonventre, Joseph V.
通讯作者：
Bonventre, Joseph V.