The effectiveness of stem cell‑derived extracellular vesicles therapy for intrauterine adhesions: a meta-analysis of preclinical studies

Abstract Background The therapeutic potential of stem cell-derived extracellular vesicles (EVs) for intrauterine adhesions (IUA) has attracted increasing preclinical investigation, yet a comprehensive and up-to-date meta-analysis is currently lacking. Before moving forward with clinical applications...

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Main Authors: Yuanyuan Sun, Yan Luo, Jinyao Ning, Yitong Chai, Jingjing Chen, Fen Xiao, Ge Li, Xu Zhou, Fen Tian, Bin Xu, Qiong Zhang, Hankun Su, Jing Zhao, Yanping Li, Hui Li
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Reproductive Biology and Endocrinology
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Online Access:https://doi.org/10.1186/s12958-025-01448-2
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author Yuanyuan Sun
Yan Luo
Jinyao Ning
Yitong Chai
Jingjing Chen
Fen Xiao
Ge Li
Xu Zhou
Fen Tian
Bin Xu
Qiong Zhang
Hankun Su
Jing Zhao
Yanping Li
Hui Li
author_facet Yuanyuan Sun
Yan Luo
Jinyao Ning
Yitong Chai
Jingjing Chen
Fen Xiao
Ge Li
Xu Zhou
Fen Tian
Bin Xu
Qiong Zhang
Hankun Su
Jing Zhao
Yanping Li
Hui Li
author_sort Yuanyuan Sun
collection DOAJ
description Abstract Background The therapeutic potential of stem cell-derived extracellular vesicles (EVs) for intrauterine adhesions (IUA) has attracted increasing preclinical investigation, yet a comprehensive and up-to-date meta-analysis is currently lacking. Before moving forward with clinical applications, it is essential to fully understand the impact of stem cell-derived EVs on IUA. Methods PubMed, EMBASE, Cochrane Library, Web of Science were searched up to May 19th 2025. Trial sequential analysis was conducted to evaluate outcomes, while sensitivity analysis and publication bias assessment were conducted using Stata 14. Results Across 26 studies (899 animals), our analyses have uncovered several important findings as the following: stem cell-derived EVs significantly improved the number of endometrial glands (SMD = 3.78; 95% CI: 2.62 ~ 4.93; P < 0.00001); endometrial thickness (SMD = 2.65; 95% CI: 1.90 ~ 3.40; P < 0.00001) and the number of embryos (SMD = 2.00; 95% CI: 1.02 ~ 2.97; P = 0.0004); fibrosis reduction (SMD = -3.25; 95% CI: -4.24~ -2.26; P < 0.00001) in IUA animal models. EVs downregulated fibrosis markers (TGF-β1, α-SMA, Col-1) and upregulated vascularization (VEGF) and proliferation (Ki67) genes. Conclusions Stem cell-derived EVs demonstrate safety and efficacy in treating IUA animal models, with potential improvements in fertility outcomes.
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spelling doaj-art-78faef550f6147adb4e5768042bc16ad2025-08-20T03:41:57ZengBMCReproductive Biology and Endocrinology1477-78272025-08-0123112010.1186/s12958-025-01448-2The effectiveness of stem cell‑derived extracellular vesicles therapy for intrauterine adhesions: a meta-analysis of preclinical studiesYuanyuan Sun0Yan Luo1Jinyao Ning2Yitong Chai3Jingjing Chen4Fen Xiao5Ge Li6Xu Zhou7Fen Tian8Bin Xu9Qiong Zhang10Hankun Su11Jing Zhao12Yanping Li13Hui Li14Department of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityAbstract Background The therapeutic potential of stem cell-derived extracellular vesicles (EVs) for intrauterine adhesions (IUA) has attracted increasing preclinical investigation, yet a comprehensive and up-to-date meta-analysis is currently lacking. Before moving forward with clinical applications, it is essential to fully understand the impact of stem cell-derived EVs on IUA. Methods PubMed, EMBASE, Cochrane Library, Web of Science were searched up to May 19th 2025. Trial sequential analysis was conducted to evaluate outcomes, while sensitivity analysis and publication bias assessment were conducted using Stata 14. Results Across 26 studies (899 animals), our analyses have uncovered several important findings as the following: stem cell-derived EVs significantly improved the number of endometrial glands (SMD = 3.78; 95% CI: 2.62 ~ 4.93; P < 0.00001); endometrial thickness (SMD = 2.65; 95% CI: 1.90 ~ 3.40; P < 0.00001) and the number of embryos (SMD = 2.00; 95% CI: 1.02 ~ 2.97; P = 0.0004); fibrosis reduction (SMD = -3.25; 95% CI: -4.24~ -2.26; P < 0.00001) in IUA animal models. EVs downregulated fibrosis markers (TGF-β1, α-SMA, Col-1) and upregulated vascularization (VEGF) and proliferation (Ki67) genes. Conclusions Stem cell-derived EVs demonstrate safety and efficacy in treating IUA animal models, with potential improvements in fertility outcomes.https://doi.org/10.1186/s12958-025-01448-2Intrauterine adhesionsExtracellular vesiclesMeta-analysisTrial sequential analysis
spellingShingle Yuanyuan Sun
Yan Luo
Jinyao Ning
Yitong Chai
Jingjing Chen
Fen Xiao
Ge Li
Xu Zhou
Fen Tian
Bin Xu
Qiong Zhang
Hankun Su
Jing Zhao
Yanping Li
Hui Li
The effectiveness of stem cell‑derived extracellular vesicles therapy for intrauterine adhesions: a meta-analysis of preclinical studies
Reproductive Biology and Endocrinology
Intrauterine adhesions
Extracellular vesicles
Meta-analysis
Trial sequential analysis
title The effectiveness of stem cell‑derived extracellular vesicles therapy for intrauterine adhesions: a meta-analysis of preclinical studies
title_full The effectiveness of stem cell‑derived extracellular vesicles therapy for intrauterine adhesions: a meta-analysis of preclinical studies
title_fullStr The effectiveness of stem cell‑derived extracellular vesicles therapy for intrauterine adhesions: a meta-analysis of preclinical studies
title_full_unstemmed The effectiveness of stem cell‑derived extracellular vesicles therapy for intrauterine adhesions: a meta-analysis of preclinical studies
title_short The effectiveness of stem cell‑derived extracellular vesicles therapy for intrauterine adhesions: a meta-analysis of preclinical studies
title_sort effectiveness of stem cell derived extracellular vesicles therapy for intrauterine adhesions a meta analysis of preclinical studies
topic Intrauterine adhesions
Extracellular vesicles
Meta-analysis
Trial sequential analysis
url https://doi.org/10.1186/s12958-025-01448-2
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