Department of Neurology, Jiangxi Provincial People's Hospital, Affiliated People's Hospital of Nanchang University, No. 152, Aiguo Road, Nanchang, 330006, Jiangxi, China.
Neurol Sci. 2021 Sep;42(9):3637-3646. doi: 10.1007/s10072-020-05036-7. Epub 2021 Jan 12.
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.
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.
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.
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.
评估间充质基质细胞（MSCs）治疗肌萎缩侧索硬化症（ALS）的临床前证据的质量，确定 MSCs 治疗的效果大小，并确定与 MSCs 效果差异相关的临床参数。
通过特定的神经行为评估，从文献中检索了 MSCs 在 ALS 动物模型中的研究。提取了 4 个主要指标（发病年龄、疾病进展减速、生存时间、危险比降低）和 14 个相对临床参数进行荟萃分析和系统评价。进行了亚组分析和荟萃回归分析，以探讨异质性的来源。
共纳入 25 项研究和 41 个独立的治疗组进行系统评价和荟萃分析。经敏感性分析校正后，发病年龄、疾病进展减速、生存时间和危险比降低的平均效应大小分别显著改善 0.28、0.25、0.54 和 0.48。进一步分析表明，动物性别这一临床参数和环孢素 A（CSA）等免疫抑制剂药物与疾病进展减速效果大小密切相关。
这些结果表明，MSCs 移植对 ALS 动物模型的神经行为改善有益，并建议在 MSCs 治疗 ALS 时，应仔细考虑并融合 MSCs 移植后的所有潜在修复作用，以最大限度地提高 MSCs 治疗的效果。
