A systematic review of published clinical studies using cell-derived extracellular vesicles: A focus on efficacy in COVID-19 and wound healing

IF 3 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine Pub Date : 2026-01-01 Epub Date: 2025-11-24 DOI:10.1016/j.retram.2025.103557

An Duong , Philippe Giguère , Risa Shorr , David S. Allan

{"title":"A systematic review of published clinical studies using cell-derived extracellular vesicles: A focus on efficacy in COVID-19 and wound healing","authors":"An Duong , Philippe Giguère , Risa Shorr , David S. Allan","doi":"10.1016/j.retram.2025.103557","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Extracellular vesicles (EVs) are nano-sized membrane-bound particles released from cells and offer promise in cell-based regenerative therapy. Preclinical research has propelled the launch of clinical trials with results from initial studies recently published. A systematic review is needed to evaluate trial designs, outcomes, product characterization and safety profiles to identify barriers and inform future research directions.</div></div><div><h3>Methods</h3><div>A systematic search of the literature was conducted (1946 to September 19, 2024) to identify clinical studies using cell-derived EVs. We extracted aspects of study design, diseases being treated, characteristics of trial subjects, isolation methods and characterization of EVs, details of product administration, main conclusions, and aspects of potential study bias.</div></div><div><h3>Results</h3><div>Twenty-five published clinical trials were included for analysis. COVID-19 and associated acute respiratory distress syndrome (ARDS) were studied most frequently (<em>n</em> = 8, 32 %). Wound healing was the second largest disease category (<em>n</em> = 5, 20 %). Seven studies (28 %) were controlled trials. Mesenchymal stromal cells (MSCs) were the most common source of EVs (20 studies, 80 %), with 494 patients receiving MSC-EVs for various indications. Most trials (68 %, <em>n</em> = 17) used ultracentrifugation as the primary method for EV isolation. An individual patient data meta-analysis of controlled COVID-19/ARDS trials investigating MSC-EVs (<em>n</em> = 3; 5 intervention groups) revealed an odds ratio (OR) for mortality of 0.46 (95 % CI 0.26 - 0.81; <em>p</em> = 0.0073). The benefits of EVs to improve wound healing are less clear with no controlled studies of MSC-EVs and no clear benefit reported in 2 controlled studies of other cell-based EVs. Although administration of EVs was generally well tolerated, safety conclusions remain preliminary given that only one serious adverse event was explicitly reported, and adverse event reporting was often incomplete.</div></div><div><h3>Conclusions</h3><div>Clinical trials of cell-derived EVs demonstrate marked heterogeneity but potential promise using MSC-EVs to treat COVID-19/ARDS, although efficacy in wound healing is less clear. More controlled studies are needed to optimize and confirm these initial results and to establish a more definitive understanding of the safety profile of EV therapy.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"74 1","pages":"Article 103557"},"PeriodicalIF":3.0000,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Research in Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452318625000662","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/11/24 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Extracellular vesicles (EVs) are nano-sized membrane-bound particles released from cells and offer promise in cell-based regenerative therapy. Preclinical research has propelled the launch of clinical trials with results from initial studies recently published. A systematic review is needed to evaluate trial designs, outcomes, product characterization and safety profiles to identify barriers and inform future research directions.

Methods

A systematic search of the literature was conducted (1946 to September 19, 2024) to identify clinical studies using cell-derived EVs. We extracted aspects of study design, diseases being treated, characteristics of trial subjects, isolation methods and characterization of EVs, details of product administration, main conclusions, and aspects of potential study bias.

Results

Twenty-five published clinical trials were included for analysis. COVID-19 and associated acute respiratory distress syndrome (ARDS) were studied most frequently (n = 8, 32 %). Wound healing was the second largest disease category (n = 5, 20 %). Seven studies (28 %) were controlled trials. Mesenchymal stromal cells (MSCs) were the most common source of EVs (20 studies, 80 %), with 494 patients receiving MSC-EVs for various indications. Most trials (68 %, n = 17) used ultracentrifugation as the primary method for EV isolation. An individual patient data meta-analysis of controlled COVID-19/ARDS trials investigating MSC-EVs (n = 3; 5 intervention groups) revealed an odds ratio (OR) for mortality of 0.46 (95 % CI 0.26 - 0.81; p = 0.0073). The benefits of EVs to improve wound healing are less clear with no controlled studies of MSC-EVs and no clear benefit reported in 2 controlled studies of other cell-based EVs. Although administration of EVs was generally well tolerated, safety conclusions remain preliminary given that only one serious adverse event was explicitly reported, and adverse event reporting was often incomplete.

Conclusions

Clinical trials of cell-derived EVs demonstrate marked heterogeneity but potential promise using MSC-EVs to treat COVID-19/ARDS, although efficacy in wound healing is less clear. More controlled studies are needed to optimize and confirm these initial results and to establish a more definitive understanding of the safety profile of EV therapy.

查看原文本刊更多论文

对已发表的使用细胞源性细胞外囊泡的临床研究的系统综述：重点关注COVID-19和伤口愈合的疗效。

背景：细胞外囊泡（EVs）是一种从细胞中释放出来的纳米级膜结合颗粒，在细胞再生治疗中具有广阔的应用前景。临床前研究推动了临床试验的启动，最近发表了初步研究的结果。需要进行系统的评价来评估试验设计、结果、产品特性和安全性概况，以确定障碍并为未来的研究方向提供信息。方法：系统检索文献（1946年至2024年9月19日），以确定使用细胞源性ev的临床研究。我们提取了研究设计、正在治疗的疾病、试验对象的特征、ev的分离方法和特征、产品给药的细节、主要结论和潜在研究偏倚的方面。结果：纳入25项已发表的临床试验进行分析。COVID-19和相关急性呼吸窘迫综合征（ARDS）的研究最为频繁（n = 8,32 %）。伤口愈合是第二大疾病类别（n = 5, 20%）。7项研究（28%）为对照试验。间充质间质细胞（MSCs）是EVs最常见的来源（20项研究，80%），494例患者因各种适应症接受了MSCs -EVs。大多数试验（68%,n = 17）使用超离心作为EV分离的主要方法。针对调查msc - ev的对照COVID-19/ARDS试验（n = 3； 5个干预组）的个体患者数据荟萃分析显示，死亡率的优势比（OR）为0.46 （95% CI 0.26 - 0.81; p = 0.0073）。电动汽车促进伤口愈合的益处尚不清楚，没有msc - ev的对照研究，也没有其他基于细胞的电动汽车的2项对照研究报告明确的益处。虽然ev的耐受性良好，但安全性结论仍然是初步的，因为只有一个严重的不良事件被明确报道，而不良事件的报告往往是不完整的。结论：细胞源性ev的临床试验显示出明显的异质性，但使用msc - ev治疗COVID-19/ARDS有潜在的前景，尽管对伤口愈合的疗效尚不清楚。需要更多的对照研究来优化和证实这些初步结果，并对EV治疗的安全性建立更明确的认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Current Research in Translational Medicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

7.00

自引率

4.90%

发文量

审稿时长

45 days

期刊介绍： Current Research in Translational Medicine is a peer-reviewed journal, publishing worldwide clinical and basic research in the field of hematology, immunology, infectiology, hematopoietic cell transplantation, and cellular and gene therapy. The journal considers for publication English-language editorials, original articles, reviews, and short reports including case-reports. Contributions are intended to draw attention to experimental medicine and translational research. Current Research in Translational Medicine periodically publishes thematic issues and is indexed in all major international databases (2017 Impact Factor is 1.9). Core areas covered in Current Research in Translational Medicine are: Hematology, Immunology, Infectiology, Hematopoietic, Cell Transplantation, Cellular and Gene Therapy.