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Human umbilical cord-derived mesenchymal stem cells alleviate valproate-induced immune stress and social deficiency
Shixiong Sun1, Shilin Luo2, Jie Chen3
1Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Insights
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) show promise for treating autism spectrum disorder (ASD). These stem cells promoted neuron growth and improved social behavior in an autism rat model by reducing brain inflammation.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Developmental Disorders
Background:
- Autism spectrum disorders (ASD) are complex neurodevelopmental conditions with limited treatment options.
- Current therapies for ASD are largely palliative, highlighting a significant unmet medical need.
- Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are being investigated for their therapeutic potential in ASD.
Purpose of the Study:
- To investigate the therapeutic effects of hUC-MSCs in a valproic acid (VPA)-induced rat model of autism.
- To explore the interaction between hUC-MSCs and cortical neurons in vitro.
- To elucidate the underlying mechanisms of hUC-MSC action in the context of neuroinflammation.
Main Methods:
- In vitro transwell migration assays were used to assess hUC-MSC and cortical neuron interactions.
- Intravenous administration of hUC-MSCs was performed in a VPA-induced rat model of autism.
- Assessment of microglial activation and behavioral testing (sociability) in VPA-exposed rats.
Main Results:
- hUC-MSCs demonstrated a positive effect on the growth of primary-cultured cortical neurons.
- Intravenous hUC-MSC administration significantly reduced microglial activation in the VPA rat model, particularly in the anterior cingulate cortex.
- Treatment with hUC-MSCs led to a significant improvement in the sociability of VPA-exposed rats.
Conclusions:
- hUC-MSCs promote neuronal growth and possess neuroprotective properties relevant to ASD.
- hUC-MSC therapy can modulate neuroinflammation, specifically microglial activation, in an autism model.
- These findings support further research into hUC-MSCs as a potential therapeutic strategy for ASD and other psychiatric disorders involving neuroinflammation.
Introduction:
Autism spectrum disorders (ASD) are a set of heterogeneous neurodevelopmental disorders characterized by impaired social interactions and stereotypic behaviors. Current clinical care is palliative at the most and there remains huge unmet medical need to fully address the core symptoms of ASD. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are emerging as a promising candidate for ASD treatment, but the precise mechanism remains controversial.
Methods:
In vitro studies we performed the transwell migration assay to explore the interaction between hUC-MSCs and the primary-cultured cortical neurons. Then we determined the therapeutic effects of intravenous administration of hUC-MSCs in rats challenged with valproic acid (VPA) during gestation, a well-defined rat model of autism.
Results:
Our studies showed that hUC-MSCs promoted the growth of primary-cultured cortical neurons. Furthermore, our results demonstrated that hUC-MSCs significantly alleviated microglial activation in the brain, especially in the anterior cingulate cortex, and effectively improved the sociability of the VPA-exposed rats.
Discussion:
These results offer valuable insights for clinical translation and further research on the mechanisms of hUC-MSCs in psychiatric disorders characterized by microglial activation, particularly in cases of autism, shall be warranted.
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