Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Stem Cells and Centre for Innovation, Canadian Blood Services, Ottawa, Canada.
Stem Cell Rev Rep. 2022 Mar;18(3):968-979. doi: 10.1007/s12015-021-10164-4. Epub 2021 Apr 24.
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.
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.
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.
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.
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).
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。
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）。
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。
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。
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）。
