A meta-analysis of efficacy in pre-clinical human stem cell therapies for traumatic brain injury
A meta-analysis of efficacy in pre-clinical human stem cell therapies for traumatic brain injury
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DOI：
10.1016/j.expneurol.2015.08.020
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发表时间：
2015-11-01
影响因子：
5.3
通讯作者：
Cummings, Brian J.
中科院分区：
文献类型：
--
作者：
Chang, Janessa;Phelan, Michael;Cummings, Brian J.
目的：评估人类细胞疗法治疗创伤性脑损伤(TBI)的临床前证据，确定修饰细胞和非修饰细胞的行为效应大小，并确定与更大效应大小相关的变量。方法：通过文献检索确定了58项使用人类干细胞进行的脑创伤动物研究。每项研究都得到了基于现有指南的质量指数(QI)评分。对最常见的行为终点：Morris水迷宫(MWM)潜伏期/正确象限和修正的神经严重程度评分(MNSS)确定细胞治疗的效果大小。结果：50项研究报告了显著的行为和/或组织学改善。未修饰细胞的MWM潜伏期的平均效应大小为-1.08，修饰细胞的平均效应尺寸为-335。MWM在正确象限内的百分比时间的平均效应大小对于未修饰细胞是1.66，对于修饰细胞是4.36。对mNSS的平均影响大小，未修饰细胞为-1.56，修饰细胞为-4.46。除了给药途径外，在方法学变量和效应大小之间没有发现显著的相关性，皮损内给药比静脉注射产生更大的效应大小。或者是脑室分娩。QI较高的研究有较小的效应量；效应量较大的研究有较大的标准误差。结论：尽管在大多数临床前文献中，人类细胞疗法研究报告改善了行为结果，但这些方法过于多样化，不利于直接比较，而且可以检测到偏差。需要复制和标准化来确定程序变量，以产生最佳结果。我们鼓励在脑外伤动物模型中使用质量标准和严谨的未来人类细胞治疗研究。(C)2015 Elsevier Inc.保留所有权利。
Objectives: Evaluate the preclinical evidence for human cell therapies for the treatment of traumatic brain injury (TBI), determine behavioral effect sizes for modified and non-modified cells, and identify variables that correlate with greater effect sizes.Methods: A literature search identified 58 animal studies of TBI using human stem cells. Each study received a Quality Index (QI) score based on existing guidelines. Effect sizes for cell therapies were determined for the most common behavioral endpoints: Morris Water Maze (MWM) latency/correct quadrant, and modified Neurological Severity Score (mNSS).Results: 50 studies reported significant behavioral and/or histological improvement. The mean effect size for MWM latency was -1.08 for non-modified cells and -335 for modified cells. The mean effect size for MWM percent time in the correct quadrant was 1.66 for non-modified cells and 4.36 for modified cells. The mean effect size on the mNSS was -1.56 for non-modified cells and -4.46 for modified cells. No significant associations were found between methodological variables and effect sizes other than route of administration, where intra-lesional delivery resulted in larger effect sizes than i.v. or ventricular delivery. Studies with higher QI had smaller effect sizes; studies with larger effect sizes had greater standard errors. QI was not associated with journal impact factor.Conclusions: Although human cell therapy studies report improved behavioral outcomes in the majority of preclinical literature, the methods are too heterogeneous to facilitate direct comparisons and bias was detected. Replication and standardization are needed to identify procedural variables to yield the best results. We encourage the use of quality criteria and rigor for future studies of human cell therapy in animal models of TBI. (C) 2015 Elsevier Inc. All rights reserved.