Introduction

Treating and preventing graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplant (HCT) remains a significant challenge. The use of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) appears promising and a systematic review of preclinical studies is needed to accelerate the design of translational studies.

Methods

We identified 4 eligible studies from a systematic review performed on December 1, 2018. In brief, eligible studies included the treatment or prevention of GVHD in animal models and the use of MSC-EVs. Study design and outcome data were extracted and reporting was evaluated using the SYRCLE tool to identify potential bias.

Results

Two studies assessed the efficacy of MSC-EVs in treatment of GVHD and 2 studies address prevention. Mice treated with MSC-EVs showed improved median survival, GVHD clinical scores and histology scores as compared to untreated mice with GVHD. Prophylactic treatment with MSC-EVs attenuated GVHD severity and improved median survival as compared to no treatment or saline.

Conclusion

Our systematic review provides important insight regarding the potential of MSC-EVs to treat or prevent GVHD. Although few studies were identified, improved survival and attenuated histologic findings of GVHD were observed in mice after MSC-EV administration for the treatment and prevention of GVHD. Dosing of EVs and route of administration remain inconsistent, however, and scalability of EV isolation for clinical studies remains a challenge. Standardized outcome reporting is needed to pool results for metanalysis.

中文翻译：

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MSC 衍生的细胞外囊泡治疗或预防移植物抗宿主病的临床前研究：文献的系统评价

介绍

异基因造血细胞移植 (HCT) 后治疗和预防移植物抗宿主病 (GVHD) 仍然是一项重大挑战。间充质基质细胞衍生的细胞外囊泡 (MSC-EV) 的使用似乎很有前景，需要对临床前研究进行系统评价，以加速转化研究的设计。

方法

我们从 2018 年 12 月 1 日进行的系统评价中确定了 4 项符合条件的研究。简而言之，符合条件的研究包括动物模型中 GVHD 的治疗或预防以及 MSC-EV 的使用。提取研究设计和结果数据，并使用 SYRCLE 工具评估报告，以确定潜在的偏倚。

结果

两项研究评估了 MSC-EV 在治疗 GVHD 中的功效，两项研究涉及预防。与未治疗的 GVHD 小鼠相比，用 MSC-EV 治疗的小鼠显示出改善的中位生存期、GVHD 临床评分和组织学评分。与未治疗或生理盐水相比，MSC-EV 的预防性治疗减轻了 GVHD 的严重程度并提高了中位生存期。

结论

我们的系统评价提供了有关 MSC-EV 治疗或预防 GVHD 潜​​力的重要见解。尽管确定的研究很少，但在给予 MSC-EV 治疗和预防 GVHD 后，在小鼠中观察到 GVHD 的存活率提高和组织学发现减弱。然而，EV 的剂量和给药途径仍然不一致，用于临床研究的 EV 分离的可扩展性仍然是一个挑战。需要标准化的结果报告来汇总结果以进行荟萃分析。