Sun Shixiong, Luo Shilin, Chen Jie, Zhang Ou, Wu Qiongying, Zeng Nianju, Bi Jinlian, Zheng Chunbing, Yan Tenglong, Li Zhiyuan, Chen Jindong, Zhang Yilei, Lang Bing
Department 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.
Department of Neurology, Xiangya Hospital of Central South University, Changsha, China.
Front Psychiatry. 2024 Aug 22;15:1431689. doi: 10.3389/fpsyt.2024.1431689. eCollection 2024.
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.
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.
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.
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.
自闭症谱系障碍（ASD）是一组异质性神经发育障碍，其特征为社交互动受损和刻板行为。目前的临床治疗最多只能起到缓解作用，在全面解决ASD的核心症状方面仍存在巨大的未满足医疗需求。人脐带间充质干细胞（hUC-MSCs）正成为ASD治疗的一个有前景的候选方案，但确切机制仍存在争议。
在体外研究中，我们进行了Transwell迁移试验，以探索hUC-MSCs与原代培养的皮质神经元之间的相互作用。然后我们确定了在孕期用丙戊酸（VPA）攻击的大鼠（一种明确的自闭症大鼠模型）中静脉注射hUC-MSCs的治疗效果。
我们的研究表明，hUC-MSCs促进了原代培养的皮质神经元的生长。此外，我们的结果表明，hUC-MSCs显著减轻了大脑中的小胶质细胞激活，尤其是在前扣带回皮质，并有效改善了VPA暴露大鼠的社交能力。
这些结果为临床转化提供了有价值的见解，对于hUC-MSCs在以小胶质细胞激活为特征的精神疾病，特别是自闭症病例中的机制进行进一步研究是必要的。
