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. 2025 Aug 13;23(1):117.
doi: 10.1186/s12958-025-01448-2.

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

Yuanyuan Sun #  1   2 , Yan Luo #  1   2 , Jinyao Ning #  1   2 , Yitong Chai  1   2 , Jingjing Chen  1   2 , Fen Xiao  3 , Ge Li  1   2 , Xu Zhou  1   2 , Fen Tian  1   2 , Bin Xu  1   2 , Qiong Zhang  1   2 , Hankun Su  1   2 , Jing Zhao  1   2 , Yanping Li  1   2 , Hui Li  4   5
Affiliations

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

Yuanyuan Sun et al. Reprod Biol Endocrinol. .

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.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12958-025-01448-2.

Keywords: Extracellular vesicles; Intrauterine adhesions; Meta-analysis; Trial sequential analysis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This article does not contain any studies involving human and animal subjects performed by any of the Authors. No ethical approval was needed for this review article. Competing interests: The authors declare no competing interests. Clinical trial registry subsections: PROSPERO registration number: CRD42024509713. Date of registration in PROSPERO: 12 March 2024.

Figures

Fig. 1
Fig. 1
Study flow diagram
Fig. 2
Fig. 2
Bibliometric analysis. (A) Citation track map. Each circle represents documents (including DOI numbers) that have been cited more than 20 times, and are defined as representative documents in the field. The larger the circle, the more times it has been cited. (B) Analysis ofannual publishing trends in PubMed database. Abbreviation: DOI: digital object unique identifier
Fig. 3
Fig. 3
An overview of studies features. Distribution of (A) publications by year (B) region (C) animal model (D) disease model (E) route of administration
Fig. 4
Fig. 4
Risk of bias summary
Fig. 5
Fig. 5
Forest plots depicting the comparison between the stem cell -derived extracellular vesicles and control groups: (A) Endometrial thickness; (B) Number of endometrial glands; (C) Fibrosis area; (D) Pregnancy rates; (E) Number of embryos
Fig. 6
Fig. 6
The illustration diagram of the mechanisms associated with IUA
Fig. 7
Fig. 7
Trial sequential analysis depicting the comparison between the stem cell-derived extracellular vesicles and control groups: (A) Number of endometrial glands. The cumulative Z curve crossed the conventional line and reached the RIS. (B) Fibrosis area. The cumulative Z curve crossed the conventional line and reached the RIS. (C) Pregnancy rates. The cumulative Z curve crossed the conventional but did not reach the RIS. (D) Endometrial thickness. The cumulative Z curve crossed the conventional but did not reach the RIS. I Number of embryos. The cumulative Z curve crossed the conventional but did not reach the RIS. Abbreviation: RIS, required information size
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