ArticleFrontiers in immunology2025
3KO-NSCs ameliorate behavioral deficits and modulate gut microbiota in a VPA-induced C57BL/6 mouse model of autism.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Continuous OFT-Based Behavioral Phenotyping Reveals Neural Stem Cell-Associated Shifts in Depression-like Mice.Brain sciences · 2026Article
- Neural Stem/Progenitor Cells Regulate Neuroinflammation: Mechanisms and Therapeutic Applications in Neurological Diseases.International journal of molecular sciences · 2026Review
- Pathophysiological roles of neural stem cells in neuropsychiatric diseases: from plasticity to pharmacological targeting.Acta pharmacologica Sinica · 2026Review
- Mesenchymal stem/stromal cell-based therapies for autism spectrum disorder: emerging evidence and clinical prospects.Journal of translational medicine · 2026Review
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Authors and funding
5 authors.
Funding
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Abstract
Background: Autism spectrum disorder (ASD) involves complex neurological and gastrointestinal pathophysiology. Existing therapies rarely address the gut-brain axis connection. This study evaluated the therapeutic potential of immune-evasive human induced pluripotent stem cell-derived neural stem cells (3KO-NSCs) in a mouse model of ASD. Methods: We used a valproic acid (VPA)-induced ASD model in C57BL/6 mice. Mice received systemic administration of 3KO-NSCs. Assessments included behavioral assays (social interaction, repetitive behaviors), hippocampal cytokine profiling (IL-6, TNF-α), 16S rRNA sequencing for gut microbiota analysis, immunohistochemistry (Iba1 Results: 3KO-hiPSC-NSC treatment significantly ameliorated VPA-induced ASD-like behaviors. It reduced hippocampal neuroinflammation (decreased IL-6 and TNF-α) and attenuated microglial overactivation (reduced Iba1+ cells), correcting synaptic pruning abnormalities. Concurrently, treatment restored gut microbiota diversity (increased Shannon index), enriching Bacteroides and reducing pro-inflammatory Proteobacteria. Conclusions: 3KO-NSCs exert dual therapeutic effects by mitigating central neuroinflammation and rebalancing gut microbiota. This provides the first direct evidence that stem cell therapy can modulate the gut-brain axis to treat ASD, positioning 3KO-NSCs as a novel bifunctional therapeutic strategy.
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