Preclinical studies of mesenchymal stem cells transplantation in amyotrophic lateral sclerosis: a systemic review and metaanalysis.

OBJECTIVES: To assess the quality of preclinical evidence for mesenchymal stromal cell (MSCs) therapy of amyotrophic lateral sclerosis (ALS), decide the effect size of MSCs treatment, and identify clinical parameters that associate with differences in MSCs effects. METHODS: A literature search identified studies of MSCs in animal models of ALS. Four main indicators (age of onset, disease progression deceleration, survival time, hazard ratio reduction) obtained through specific neurobehavioral assessment, and 14 relative clinical parameters were extracted for metaanalysis and systematic review. Subgroup analysis and metaregression were performed to explore sources of heterogeneity. RESULTS: A total of 25 studies and 41 independent treated arms were used for systematic review and metaanalysis. After adjusted by sensitivity analysis, the mean effect sizes were significantly improved by 0.28 for the age of onset, 0.25 for the disease progression deceleration, 0.54 for the survival time, and 0.48 for hazard ratio reduction. With further analysis, we demonstrated that both the clinical parameter of animal gender and immunosuppressive drug of cyclosporin A (CSA) had a close correlation with disease progression deceleration effect size. CONCLUSIONS: These results showed that MSCs transplantation was beneficial for neurobehavioral improvement in the treatment of ALS animal model and recommended that all potential reparative roles of MSCs postdelivery, should be carefully considered and fused to maximize the effectiveness of MSCs therapy in ALS.