Systematic review and meta-analysis of efficacy of mesenchymal stem cells on locomotor recovery in animal models of traumatic brain injury

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.

One Step at a Time, Stem Cell Therapy for Traumatic Brain Injury Needs Two More Breakthroughs

“…69 Few reports have demonstrated integration of such cells into host tissues, thus suggesting this cell type to be a poor candidate for cell replacement. [70][71][72][73] A recent study with athymic rat TBI and hNSCs ~38% of the transplanted cells expressed NeuN. 74 The duration of differentiation of hNSCs into NeuN positive cells is consistent with a published report that showed ~6-8 weeks were sufficient to induce transplant derived neurogenesis.…”

Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2D and 3D conditions improves functional recovery in rats after traumatic brain injury

“…MSCs alone and MSCs seeded into scaffolds improve functional outcome in animal models of stroke and TBI (Kim et al, 2010; Lu et al, 2007; Mahmood et al, 2004a; Mahmood et al, 2005, 2007; Mahmood et al, 2014a; Mahmood et al, 2014b; Peng et al, 2015; Qu et al, 2011; Qu et al, 2008; Xiong et al, 2009). The mechanisms underlying improvement in MSC-induced functional recovery after TBI are not clear.…”

Preclinical progenitor cell therapy in traumatic brain injury: a meta-analysis

“…There are two other meta-analyses that evaluate progenitor cell treatment for traumatic brain injury. In the analysis by Peng et al (55) only behavioral data were extracted from studies in animals that received only human mesenchymal stromal cells (hMSC), limiting the number of studies that could be included. In the meta-analysis by Chang et al (56) studies were included that examined modified and naïve progenitor cells for the treatment of traumatic brain injury.…”

“…Peng et al . ran a stratified meta-analysis, and found that the quality score of 5 (possible scores from 0–10) correlated with the largest effect sizes (62). However, neither of these meta-analyses used the same quality metrics.…”