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.

中文翻译：

---

间充质干细胞移植治疗肌萎缩侧索硬化症的临床前研究：系统评价和荟萃分析

目标

评估间充质基质细胞 (MSC) 治疗肌萎缩侧索硬化症 (ALS) 的临床前证据的质量，确定 MSC 治疗的效果大小，并确定与 MSC 效果差异相关的临床参数。

方法

文献检索发现了 ALS 动物模型中 MSC 的研究。通过特定的神经行为评估获得4个主要指标（发病年龄、疾病进展减慢、生存时间、风险比降低），并提取14个相关临床参数进行荟萃分析和系统评价。进行亚组分析和元回归来探索异质性的来源。

结果

总共 25 项研究和 41 个独立治疗组用于系统评价和荟萃分析。经过敏感性分析调整后，发病年龄的平均效应值显着提高了0.28，疾病进展减慢的平均效应值显着提高了0.25，生存时间的平均效应值显着提高了0.54，风险比降低的平均效应值显着提高了0.48。通过进一步分析，我们证明动物性别和免疫抑制剂环孢素A（CSA）的临床参数与疾病进展减速效应大小密切相关。

结论

这些结果表明，间充质干细胞移植有利于治疗 ALS 动物模型的神经行为改善，并建议应仔细考虑和融合间充质干细胞在分娩后的所有潜在修复作用，以最大限度地发挥间充质干细胞治疗 ALS 的有效性。