MSC 衍生的细胞外囊泡治疗糖尿病创面：临床前动物研究的系统评价和荟萃分析。

MSC-Derived Extracellular Vesicles to Heal Diabetic Wounds: a Systematic Review and Meta-Analysis of Preclinical Animal Studies.

机构信息

Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Stem Cells and Centre for Innovation, Canadian Blood Services, Ottawa, Canada.

出版信息

Stem Cell Rev Rep. 2022 Mar;18(3):968-979. doi: 10.1007/s12015-021-10164-4. Epub 2021 Apr 24.

DOI:10.1007/s12015-021-10164-4

PMID:33893619

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8064883/

Abstract

INTRODUCTION

Extracellular vesicles from mesenchymal stromal cells (MSC-EVs) have shown promise in wound healing. Their use in diabetic wounds specifically, however, remains pre-clinical and their efficacy remains uncertain less clear. A systematic review of preclinical studies is needed to determine the efficacy of MSC-EVs in the treatment of diabetic wounds to accelerate the clinical translation of this cell-based therapy.

METHODS

PubMed and Embase were searched (to June 23, 2020). All English-language, full-text, controlled interventional studies comparing MSC-EVs to placebo or a "no treatment" arm in animal models of diabetic wounds were included. Study outcomes, including wound closure (primary outcome), scar width, blood vessel number and density, and re-epithelialisation were pooled using a random effects meta-analysis. Risk of bias (ROB) was assessed using the SYRCLE tool for pre-clinical animal studies.

RESULTS

A total of 313 unique records were identified from our search, with 10 full text articles satisfying inclusion criteria (n = 136 animals). The administration of MSC-EVs improved closure of diabetic wounds compared to controls with a large observed effect (Standardized Mean Difference (SMD) 5.48, 95% Confidence Interval (CI) 3.55-8.13). Healing was further enhanced using MSC-EVs enriched in non-coding RNAs or microRNAs compared to controls (SMD 9.89, 95%CI 7.32-12.46). Other outcomes, such as blood vessel density and number, scar width, and re-epithelialisation were improved with the administration of MSC-EVs, with a large effect. ROB across studies was unclear.

CONCLUSION

MSC-EVs, particularly following enrichment for specific RNAs, are a promising treatment for diabetic wounds in pre-clinical studies and translation to the clinical domain appears warranted.

REGISTRATION

PROSPERO #CRD42020199327 [248]. Forest plot demonstrating increased wound closure rates of diabetic wounds receiving genetically modified MSC-EVs that were enriched for specific RNAs. DFO = deferoxamine. Control groups were inactive (no treatment or saline) except for 3 studies which used hydrogels without MSC-EVs as control (Li M 2016; Shi 2017; Tao 2016).

摘要

简介

间充质基质细胞（MSC）的细胞外囊泡（EVs）在伤口愈合方面显示出了良好的效果。然而，它们在糖尿病伤口中的应用仍然处于临床前阶段，其疗效尚不确定。因此，需要对临床前研究进行系统评价，以确定 MSC-EVs 在治疗糖尿病伤口中的疗效，从而加速这种基于细胞的治疗方法的临床转化。

方法

检索了 PubMed 和 Embase（截至 2020 年 6 月 23 日）。纳入了所有比较 MSC-EVs 与安慰剂或糖尿病伤口动物模型中“无治疗”组的英文全文、对照干预研究。使用随机效应荟萃分析汇总了包括伤口闭合（主要结局）、瘢痕宽度、血管数量和密度以及再上皮化在内的研究结局。使用 SYRCLE 工具评估了临床前动物研究的偏倚风险（ROB）。

结果

从我们的检索中总共确定了 313 条独特的记录，其中 10 篇全文文章符合纳入标准（n=136 只动物）。与对照组相比，MSC-EVs 的给药可改善糖尿病伤口的闭合，具有较大的观察效果（标准化均数差（SMD）5.48，95%置信区间（CI）3.55-8.13）。与对照组相比，用非编码 RNA 或 microRNAs 富集的 MSC-EVs 治疗可进一步增强愈合效果（SMD 9.89，95%CI 7.32-12.46）。其他结局，如血管密度和数量、瘢痕宽度和再上皮化，也得到了改善，效果显著。各研究的 ROB 不明确。

结论

在临床前研究中，MSC-EVs，特别是经特定 RNA 富集后，是治疗糖尿病伤口的一种有前途的方法，有必要将其转化到临床领域。

登记

PROSPERO #CRD42020199327 [248]。森林图显示接受基因修饰的 MSC-EVs 治疗的糖尿病伤口的闭合率增加，这些 MSC-EVs 经特定 RNA 富集。DFO=去铁胺。对照组为无活性（无治疗或生理盐水），除 3 项研究外，这些研究使用无 MSC-EVs 的水凝胶作为对照（Li M 2016；Shi 2017；Tao 2016）。