Therapeutic potential of mesenchymal stem cells in acute kidney injury is affected by administration timing
Therapeutic potential of mesenchymal stem cells in acute kidney injury is affected by administration timing
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间充质干细胞在急性肾损伤中的治疗潜力受给药时机的影响
DOI：
10.1093/abbs/gmx016
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发表时间：
2017-04-01
影响因子：
3.7
通讯作者：
Ding, Xiaoqiang
中科院分区：
文献类型：
--
作者：
Liu, Xiaoyan;Cai, Jieru;Ding, Xiaoqiang
间充质干细胞（MSC）移植是治疗急性肾损伤的一种很有前途的方法。然而，由于移植后存活率较差，其疗效有限。在这项研究中，我们研究了骨髓间充质干细胞移植时间如何影响肾缺血再灌注（I/R）损伤模型中骨髓间充质干细胞的存活和治疗潜力。在肾I/R损伤后，炎症过程和组织损伤在I/R后1周内被表征，我们发现炎症在I/R后12-24小时达到顶峰（h.p.i.），尿中性粒细胞明胶酶相关脂钙素（NGAL）的测量与炎症的测量高度相关。我们用不同时间点收集的I/R损伤肾组织匀浆的上清液培养MSCs，发现12和24 hp / I的肾匀浆对MSCs毒性最大，而1 hp / I的匀浆对MSCs的细胞毒性不如12和24 hp / I的。与12或24 hp / I给药的MSCs相比，缺血或1 hp / I后立即给药的细胞具有最高的肾保护和抗炎作用。我们的研究结果表明，在形成强炎症微环境之前应用MSC治疗急性肾损伤是最有效的，尿液NGAL可能有助于检测I/R肾损伤的炎症和选择MSC移植时机。
Mesenchymal stem cell (MSC) transplantation is a promising therapy for acute kidney injury; however, the efficacy is limited due to poor survival after transplantation. In this study, we investigated how MSC transplantation timing affected the survival and therapeutic potential of MSCs in the kidney ischemia-reperfusion (I/R) injury model. After kidney I/R injury, the inflammatory process and tissue damage were characterized over 1 week post-I/R, we found that inflammation peaked at 12-24 h post-I/R (h.p.i.), and urine neutrophil gelatinase-associated lipocalin (NGAL) measurements correlated highly with measures of inflammation. We cultured MSCs with supernatants from I/R injured kidney tissue homogenates collected at different time points and found that kidney homogenates from 12 and 24 h.p.i. were most toxic to MSCs, whereas homogenates from 1 h.p.i. were not as cytotoxic as those from 12 and 24 h.p.i. Compared with MSCs administered at 12, or 24 h.p.i., cells administered immediately after ischemia or 1 h.p.i. yielded the highest renoprotective and anti-inflammatory effects. Our findings indicate that MSC treatment for acute kidney injury is most effective when applied prior to the development of a potent inflammatory microenvironment, and urine NGAL may be helpful for detecting inflammation and selecting MSC transplantation timing in I/R kidney injury.