Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles as a Cell-Free Approach in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis of Preclinical Studies

19/09/2026

AI Summary

MSC-EVs significantly improved sociability and reduced repetitive behaviours in preclinical ASD models, with large standardised effect sizes.
MSC-EV treatment modulated neuroinflammation: decreased IL‑1, TNF‑alpha, IL‑6 and increased anti-inflammatory IL‑10.
Umbilical cord and adipose-derived MSC-EVs showed superior efficacy; however standardised protocols and more preclinical studies are required for translation.

TL;DR (AI Generated)

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) offer a promising cell-free therapy due to their immunomodulatory and regenerative properties.

MSC-EV-treated mice showed significant improvements in sociability (SMD =1.34, 95% CI:0.68-2.76), reduced repetitive behaviors (SMD =-1.12, 95% CI:-0.65 to -1.59), and modulated neuroinflammation, with decreased pro-inflammatory cytokines (IL-1, SMD = -2.28, 95% CI:-0.33 to -4.24 and TNF-a, SMD = -1.22, 95% CI:-0.47 to -1.97 and IL-6, SMD = -1.03, 95% CI:-0.38 to -1.68) and increased IL-10 (SMD =0.58, 95% CI:0.03 to 1.13).

CONCLUSION: MSC-EVs demonstrate significant therapeutic potential in preclinical ASD models by improving core symptoms and modulating inflammation.

Basic summary

Behav Brain Res. 2026 Sep 18:116478. doi: 10.1016/j.bbr.2026.116478. Online ahead of print.

ABSTRACT

BACKGROUND: Autism Spectrum Disorder (ASD) is an intricate neurodevelopmental condition distinguished by challenges in social interaction, repetitive behavioral patterns, and neuroinflammation, with limited effective treatments. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) offer a promising cell-free therapy due to their immunomodulatory and regenerative properties. This study evaluates their therapeutic efficacy in preclinical ASD models.

METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis, searching PubMed, Embase, Scopus, and Web of Science. The SYRCLE tool assessed risk of bias. Standardized mean difference (SMD) was calculated using a random-effects model to evaluate MSC-EV effects on sociability, repetitive behaviors, and inflammatory cytokines. Subgroup analysis, sensitivity analysis, and publication bias assessment addressed heterogeneity.

RESULTS: Five studies (2018-2024) were included. MSC-EV-treated mice showed significant improvements in sociability (SMD =1.34, 95% CI:0.68-2.76), reduced repetitive behaviors (SMD =-1.12, 95% CI:-0.65 to -1.59), and modulated neuroinflammation, with decreased pro-inflammatory cytokines (IL-1, SMD = -2.28, 95% CI:-0.33 to -4.24 and TNF-a, SMD = -1.22, 95% CI:-0.47 to -1.97 and IL-6, SMD = -1.03, 95% CI:-0.38 to -1.68) and increased IL-10 (SMD =0.58, 95% CI:0.03 to 1.13). Subgroup analysis indicated umbilical cord- and adipose-derived MSC-EVs had superior efficacy.

CONCLUSION: MSC-EVs demonstrate significant therapeutic potential in preclinical ASD models by improving core symptoms and modulating inflammation. However, limited studies and heterogeneity highlight the need for standardized protocols and further preclinical research to facilitate clinical translation.

PMID:42759891 | DOI:10.1016/j.bbr.2026.116478

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