Umbrella review of mesenchymal stem cell-derived extracellular vesicles in preclinical models: therapeutic efficacy across diverse conditions
Mussin N.M. Zhilisbayeva K.R. Baspakova A. Kurmanalina M.A. Tamadon A.
2025Frontiers Media SA
Frontiers in Cell and Developmental Biology
2025#13
Background: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapeutic strategy for various diseases due to their anti-inflammatory, anti-apoptotic, and regenerative properties. Numerous meta-analyses have evaluated MSC-EV efficacy in preclinical animal models, but a comprehensive synthesis across diverse conditions is lacking. Objective: This umbrella review aims to systematically evaluate the therapeutic efficacy, mechanisms, and methodological quality of MSC-EVs in preclinical models across multiple diseases. Methods: A systematic search of Scopus and Web of Science was conducted to identify meta-analyses published up to July 2025, focusing on MSC-EV interventions in preclinical animal models. Data were extracted on study characteristics, exosome sources, animal models, outcomes, and risk of bias. The AMSTAR 2 tool assessed meta-analysis quality, while SYRCLE and CAMARADES tools evaluated primary study bias. Narrative and quantitative syntheses summarized efficacy, heterogeneity, and publication bias. Results: Forty-seven meta-analyses covering 27 diseases were included, spanning neurological, renal, wound healing, liver, musculoskeletal, respiratory, and reproductive disorders. MSC-EVs demonstrated high efficacy, significantly improving functional scores, reducing inflammation, and promoting regeneration. Bone marrow-, adipose-, and umbilical cord-derived EVs were most effective, with modified EVs showing enhanced outcomes. Methodological quality was moderate (AMSTAR 2), with high heterogeneity (I2 > 70%) and frequent risk of bias due to poor randomization and blinding. Publication bias was noted but often robust after adjustments. Conclusion: MSC-EVs exhibit robust therapeutic potential across diverse preclinical models, supporting their development as a versatile regenerative therapy. Standardization of EV protocols, improved study quality, and mechanistic insights are critical for clinical translation. This review provides a comprehensive framework for advancing MSC-EV research and application. Copyright
exosomes , extracellular vesicles , mesenchymal stem cells , preclinical models , regenerative medicine , umbrella review
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Department of General Surgery No. 2, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of Languages, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of Epidemiology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of Dental Disciplines and Maxillofacial Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of General Surgery No. 2
Department of Languages
Department of Epidemiology
Department of Dental Disciplines and Maxillofacial Surgery
Department of Natural Sciences
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