Mesenchymal Stem Cell-derived Extracellular Vesicles Therapy for Primary Ovarian Insufficiency: a Systematic Review and Meta-analysis of Pre-clinical Studies

Overview

Journal J Ovarian Res

Publisher Biomed Central

Specialties Gynecology & Obstetrics
Reproductive Medicine

Date 2024 Oct 14

PMID 39402602

Authors

Shahryar Rajai Firouzabadi

Ida Mohammadi

Kiana Ghafourian

Seyed Ali Mofidi

Shahrzad Rajaei Firouzabadi

Seyed Mahmoud Hashemi

Fahimeh Ramezani Tehrani

Kyana Jafarabady

Affiliations

Soon will be listed here.

Abstract

Background: Primary ovarian insufficiency (POI) manifests with hormonal imbalances, menstrual irregularities, follicle loss, and infertility. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are emerging as a promising treatment for POI. This systematic review aims to assess the effects of MSC-EVs on follicle number, hormonal profile, and fertility in POI animal models.

Methods: A systematic search of PubMed, Scopus, and Web of Science databases up to December 14th, 2023 was conducted. Two reviewers independently conducted screening, risk of bias assessment, and data extraction. Meta-analysis was performed to analyze treatment versus control outcomes using a random effects model. Publication bias was assessed using Egger's regression test and sensitivity analysis was assessed using the leave-one-out method. Subgroup analyses and meta-regressions were conducted based on EV source, induction model, type of animal, study quality, administration route, administration frequency and route, and dose.

Results: a total of 29 studies were included. MSC-EVs treatment significantly increased total follicle count (SMD, (95CI), p-value; 3.56, (0.91, 6.21), < 0.001), including primordial (SMD, (95CI), p-value; 2.86, (1.60, 4.12), < 0.001), primary (SMD, (95CI), p-value; 3.17, (2.28, 4.06), < 0.001), mature (SMD, (95CI), p-value; 2.26, (1.02, 3.50), < 0.001), and antral follicles (SMD, (95CI), p-value; 2.44, (1.21, 3.67), < 0.001). Administration frequency and route did not affect this outcome, but EV source affected primordial, primary, secondary and antral follicle count. Additionally, MSC-EVs treatment elevated anti-müllerian hormone (SMD, (95CI); 3.36, (2.14, 4.58)) and estradiol (SMD, (95CI); 3.19, (2.20, 4.17)) levels while reducing follicle stimulating hormone levels (SMD, (95CI); -2.68, (-4.42, -0.94)). Unlike EV source, which had a significant impact on all three hormones, administration frequency, route, and EV dose did not affect this outcome. Moreover, treatment increased offspring number (SMD, (95CI); 3.70, (2.17, 5.23)) and pregnancy odds (OR, (95CI); 10.25, (4.29, 24.46)) compared to controls. Publication bias and a high level of heterogeneity was evident in all analyses, except for the analysis of the pregnancy odds. However, sensitivity analysis indicated that all of the analyses were stable.

Conclusion: MSC-EVs therapy shows promise for POI treatment, potentially facilitating clinical translation. However, Further research is warranted to optimize methodology and assess side effects.

Citing Articles

Mesenchymal Stem Cells: What We Have Learned and How to Manage Them.

Lampiasi N Biology (Basel). 2025; 14(1).

PMID: 39857232 PMC: 11762337. DOI: 10.3390/biology14010001.

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