Abstract
IntroductionThe therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. Conducting systematic review and meta-analyses based on data from animal studies can be used to inform clinical trial design. To conduct a systematic review and meta-analysis to (i) systematically review the literatures describing the effect of MSCs therapy in animal models of TBI, (ii) determine the estimated effect size of functional locomotor recovery after experimental TBI, and (iii) to provide empirical evidence of biological factors associated with greater efficacy.MethodsWe conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the efficacy of MSCs in animal models of TBI. Two investigators independently assessed the identified studies. We extracted the details of individual study characteristics from each publication, assessed study quality, evaluated the effect sizes of MSCs treatment, and performed stratified meta-analysis and meta-regression, to assess the influence of study design on the estimated effect size. The presence of small effect sizes was investigated using funnel plots and Egger’s tests.ResultsTwenty-eight eligible controlled studies were identified. The study quality was modest. Between-study heterogeneity was large. Meta-analysis showed that MSCs exert statistically significant positive effects on sensorimotor and neurological motor function. For sensorimotor function, maximum effect size in studies with a quality score of 5 was found in the weight-drop impact injury TBI model established in male SD rats, to which syngeneic umbilical cord-derived MSCs intracerebrally at cell dose of (1–5) × 106 was administered r 6 hours following TBI, using ketamine as anesthetic agent. For neurological motor function, effect size was maximum for studies with a quality score of 5, in which the weight-drop impact injury TBI models of the female Wistar rats were adopted, with administration syngeneic bone marrow-derived MSCs intravenously at cell dose of 5 × 106 at 2 months after TBI, using sevofluorane as anesthetic agent.ConclusionsWe conclude that MSCs therapy may improve locomotor recovery after TBI. However, additional well-designed and well-reported animal studies are needed to guide further clinical studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0034-0) contains supplementary material, which is available to authorized users.
Highlights
The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive
Systematic reviews and meta-analyses of animal experiments allow for a more objective appraisal of the research evidence than is allowed by the traditional narrative reviews more commonly associated with animal research, and offer a sensible and rational approach to assess the translational potential of promising experimental interventions before decisions are made to proceed with clinical trials [76]
From the results of our randomeffects meta-analysis, we conclude that MSCs might be beneficial in treating experimental TBI in terms of improving sensorimotor and neurological motor function, indicating that MSCs might be a potentially new candidate for neuroprotective activity in the context of TBI
Summary
The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. The beneficial effects of mesenchymal stem cell (MSC)-based therapy for acute neurological injuries in animal models, like TBI [6], have drawn more and more attention. MSCs present relative ease of isolation, efficient ex vivo expansion, lack of ethical concerns, and acceptable safety [16,17,18,19] All of these features make MSCs an ideal therapeutic regimen to treat various injuries including stroke [20,21], myocardial infarction [22], acute lung injury [23], and TBI [24]. An increasing number of rodent studies have investigated the efficacy of MSCs on neurological recovery, a relevant clinical outcome that is considered pivotal among TBI patients [27,28,29]
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