Zhang Guangyuan, Wang Dandan, Miao Shuai, Zou Xiangyu, Liu Guohua, Zhu Yingjian
Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
Department of Nephrology, The Second People's Hospital of Shenzhen, Guangzhou Medical University, Shenzhen, Guangzhou, Guangdong 510182, P.R. China.
Exp Ther Med. 2016 Apr;11(4):1519-1525. doi: 10.3892/etm.2016.3076. Epub 2016 Feb 16.
The potential involvement of the endocrine/paracrine mechanisms in the mesenchymal stromal cells (MSCs) therapy for acute kidney injury (AKI) has been increasingly studied. The aim of the present meta-analysis was to systematically review the therapeutic role of MSC-conditioned medium (CM) or MSCs released by extracellular vesicles (Evs) for the treatment of AKI in rodent models. Studies were identified using PubMed and Scopus databases using a custom search strategy and eligibility criteria. Data regarding serum creatinine (SCr) concentration, CM or Evs, measurement time point, AKI model (toxic or non-toxic) and other parameters, including delivery route, animal type and animal numbers, were extracted. Pooled analysis and subgroup analysis as well as multivariable meta-regression were performed. Heterogeneity and publication bias were also investigated. A total of 13 studies were included and analyzed. Pooled analysis showed reduced SCr (0.93 [0.67, 1.20], mg/dl) in rodent models of AKI after CM/Evs therapy. The results of the subgroup analysis suggested that Evs induced an increased therapeutic effect, in the form of SCr reduction, as compared with CM (P=0.05). There were also other significant influential factors for SCr reduction including measurement time point (P=0.0004) and therapeutic time point (P<0.0001) after surgery. By contrast, parameters such as delivery route, injury type and cell type were not significant influential factors. Multivariable meta-regression analysis showed that measurement time point (P=0.041), therapeutic time point (P=0.03), Evs or CM (P=0.0003) and cell type (P<0.0001) were influential factors in the reduction of SCr. The present meta-analysis indicates that CM or Evs derived from MSCs are able to improve the impaired renal function in rodents modelling AKI. Compared with CM, Evs may produce a more marked therapeutic effect in recovery from renal failure. In addition, CM or Evs administration in early stages of AKI may result in more evident effects.
内分泌/旁分泌机制在间充质基质细胞（MSCs）治疗急性肾损伤（AKI）中的潜在作用已得到越来越多的研究。本荟萃分析的目的是系统评价MSCs条件培养基（CM）或细胞外囊泡（Evs）释放的MSCs对啮齿动物模型中AKI的治疗作用。使用定制的搜索策略和纳入标准，通过PubMed和Scopus数据库检索相关研究。提取有关血清肌酐（SCr）浓度、CM或Evs、测量时间点、AKI模型（毒性或非毒性）以及其他参数（包括给药途径、动物类型和动物数量）的数据。进行了汇总分析、亚组分析以及多变量Meta回归分析。还调查了异质性和发表偏倚。共纳入并分析了13项研究。汇总分析显示，CM/Evs治疗后，AKI啮齿动物模型中的SCr降低（0.93 [0.67, 1.20]，mg/dl）。亚组分析结果表明，与CM相比，Evs以SCr降低的形式诱导了更高的治疗效果（P = 0.05）。SCr降低还有其他显著影响因素，包括测量时间点（P = 0.0004）和手术后的治疗时间点（P < 0.0001）。相比之下，给药途径、损伤类型和细胞类型等参数不是显著影响因素。多变量Meta回归分析显示，测量时间点（P = 0.041）、治疗时间点（P = 0.03）、Evs或CM（P = 0.0003）以及细胞类型（P < 0.0001）是SCr降低的影响因素。本荟萃分析表明，源自MSCs的CM或Evs能够改善AKI啮齿动物模型中受损的肾功能。与CM相比，Evs在肾衰竭恢复中可能产生更显著的治疗效果。此外，在AKI早期给予CM或Evs可能会产生更明显的效果。
