‌Dual-target hUCMSCs/EVs therapy for autism spectrum disorder: remodeling gut microbiota and modulating neuroimmune crosstalk in a valproic acid-induced C57BL/6 mice model.

Researchers tested a new treatment approach for autism using stem cells from umbilical cords along with tiny particles they produce. In mice with autism-like symptoms, the combination treatment worked better than either treatment alone. It improved social behaviors, reduced brain inflammation, and restored healthy gut bacteria. While this is early research in animals, it suggests targeting both the brain and gut together might be a promising future treatment approach for autism.

This preclinical study investigated a dual-target therapy combining human umbilical cord mesenchymal stem cells (hUCMSCs) with their extracellular vesicles (EVs) in a valproic acid-induced autism mouse model. While individual treatments showed some benefits, the combination therapy demonstrated superior efficacy across multiple domains including social behavior and repetitive behaviors. The combined approach normalized neuroinflammatory markers, reduced oxidative stress, restored brain structure, and improved gut microbiota composition by increasing beneficial bacteria like Lactobacillus. The study suggests this dual-target strategy addresses the neuro-immune-microbiota axis implicated in autism pathogenesis, offering a potentially promising translational approach for autism treatment.

This preclinical research suggests dual-target approaches addressing both neuroimmune dysfunction and gut microbiota may be more effective than single interventions. However, extensive human trials are needed before clinical application. The findings support further investigation of stem cell-based therapies and gut-brain axis interventions for autism treatment.

This is a preclinical study in mice using a valproic acid-induced autism model. Sample sizes are not reported. Translation to human autism may differ significantly. Long-term effects and safety profiles are unknown. The study lacks control for potential placebo effects of combined interventions.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. Accumulating evidence implicates neuroimmune dysregulation and gut microbiota dysbiosis in its pathogenesis, yet effective therapies targeting these mechanisms are lacking. This study investigated the therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) and their extracellular vesicles (EVs), both alone and in combination, in a valproic acid (VPA)-induced ASD mouse model. VPA-exposed C57BL/6 mice were randomized into five groups: control, VPA, hUCMSCs alone, EVs alone, and hUCMSCs + EVs combination.

Behavioral tests, biochemical analyses, 16 S rRNA sequencing, immunofluorescence, and transmission electron microscopy (TEM) were performed RESULTS: While both hUCMSCs and EVs alone showed some beneficial effects on certain ASD-like symptoms, each exhibited limited efficacy in achieving comprehensive remediation. In contrast, the combined hUCMSCs + EVs therapy yielded the most robust improvements across multiple domains, including social interaction and repetitive behaviors. Furthermore, the combination therapy synergistically normalized neuroinflammatory cytokine levels and oxidative stress, restored synaptic and mitochondrial ultrastructure in key brain regions, and promoted gut microbiota homeostasis by enriching beneficial bacteria such as Lactobacillus and reducing pathogens. These results highlight that although individual treatments offer partial relief, only the combined strategy fully restores neuroimmune-microbiota homeostasis, demonstrating a complementary and synergistic therapeutic effect.

This study establishes a novel dual-target approach leveraging systemic hUCMSCs and CNS-targeted EVs, providing a promising translational strategy for ASD through orchestrated regulation of the neuro-immune-microbiota axis.