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Published on: July 11, 2025
Human Umbilical Cord Blood Mesenchymal Stem Cells Ameliorate Autism-Like Behaviors in a Valproic Acid-Induced Mouse
Jie Tian1,2,3, Hujing Deng1,2,4, Zhoujing Hu1
1Department of Pediatrics, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Insights
Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) show promise in treating autism spectrum disorder (ASD) in mice. This study found hUC-MSCs improved social behaviors and reduced repetitive actions, offering a potential new therapy for ASD.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Developmental Biology
Background:
- Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with limited pharmacological treatments.
- Investigating novel therapeutic avenues is crucial for improving the quality of life for individuals with ASD.
Purpose of the Study:
- To evaluate the therapeutic efficacy and safety of human umbilical cord blood mesenchymal stem cells (hUC-MSCs) in an autism spectrum disorder (ASD) mouse model.
- To elucidate the underlying mechanisms of hUC-MSC action in mitigating ASD-like behaviors.
Main Methods:
- Utilized a valproic acid (VPA)-induced mouse model of ASD.
- Administered hUC-MSCs and assessed safety via H&E staining and monitored overall health.
- Conducted behavioral analyses for social interaction, repetitive behaviors, and anxiety, alongside molecular analyses (RT-PCR, Western blot).
Main Results:
- hUC-MSCs significantly alleviated behavioral abnormalities in the VPA-induced ASD mouse model without adverse effects.
- Treatment promoted cortical neuronal dendritic development and restored the IGF-1R/Akt signaling pathway.
- Upregulated synaptic plasticity genes (GAP-43, SYP) and IL-10, while downregulating proapoptotic (Bax, Caspase-3) and pro-inflammatory (IL-6, IL-1β) markers.
Conclusions:
- hUC-MSCs exert neuroprotective effects via the IGF-1/Akt pathway, enhancing neuronal development and reducing neuroinflammation and apoptosis.
- Potential therapeutic benefits are linked to paracrine factors or gene expression regulation by hUC-MSCs.
- Findings support hUC-MSCs as a potential novel stem cell therapy for ASD, offering new insights into its pathogenesis.
Background:
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that significantly impacts children's physical and mental health, yet effective pharmacological treatments remain limited. The primary objective of this study was to investigate the therapeutic effects of human umbilical cord blood mesenchymal stem cells (hUC-MSCs) on ASD, evaluate the safety profile of hUC-MSCs, and elucidate their underlying mechanisms and functional roles.
Methods:
In this study, we utilized the offspring of pregnant mice exposed to valproic acid (VPA) as an animal model of ASD. At the beginning of 5 weeks of age, 5 × 105 hUC-MSCs were administered into the lateral ventricles to evaluate their safety profile and elucidate their potential roles and underlying mechanisms. Specifically, we first monitored the growth and overall health status of the mice following hUC-MSC treatment and assessed potential toxic effects by performing H&E staining on major organs. Second, behavioral analyses were conducted to examine changes in social interaction, repetitive and stereotyped behaviors, and anxiety-like behaviors in young mice before and after hUC-MSC intervention. Finally, the mechanisms underlying the therapeutic effects of hUC-MSCs in ASD were explored using techniques such as RT-PCR, Western blot analysis, brain tissue staining, and neuron culture experiments.
Results:
Here, we demonstrate that hUC-MSCs effectively mitigate behavioral abnormalities in a VPA-induced mouse model of autism without notable adverse effects. Mechanistically, hUC-MSC treatment promotes cortical neuronal dendritic development and restores the phosphorylation levels of insulin-like growth factor 1 receptor (IGF-1R) and protein kinase B (Akt). Furthermore, mRNA expression of synaptic plasticity-associated genes GAP-43 and SYP, as well as the anti-inflammatory cytokine IL-10, was significantly upregulated, while the expression of proapoptotic genes Bax and Caspase-3, along with pro-inflammatory cytokines IL-6 and IL-1β, was markedly suppressed.
Conclusions:
These findings suggest that hUC-MSCs may exert neuroprotective effects by modulating the IGF-1/Akt signaling pathway, promoting neuronal development, reducing neuroinflammation, and inhibiting apoptosis, ultimately alleviating core ASD-like symptoms. The therapeutic benefits may stem from paracrine factors secreted by hUC-MSCs or their ability to regulate gene expression linked to neuronal development. Our study provides new insights into ASD pathogenesis and highlights the potential of hUC-MSCs as a novel stem cell-based therapy for ASD.
