Tamouza Ryad, Volt Fernanda, Richard Jean-Romain, Wu Ching-Lien, Bouassida Jihène, Boukouaci Wahid, Lansiaux Pauline, Cappelli Barbara, Scigliuolo Graziana Maria, Rafii Hanadi, Kenzey Chantal, Mezouad Esma, Naamoune Soumia, Chami Leila, Lejuste Florian, Farge Dominique, Gluckman Eliane
Translational Neuropsychiatry, INSERM, IMRB, DMU, AP-HP, Univ Paris Est Créteil, Créteil, France.
Institut de Recherche Saint Louis (IRSL), Eurocord, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.
Front Cell Dev Biol. 2022 Jul 5;10:809686. doi: 10.3389/fcell.2022.809686. eCollection 2022.
Autism spectrum disorder (ASD) represents a set of heterogeneous neurodevelopmental conditions defined by impaired social interactions and repetitive behaviors. The number of reported cases has increased over the past decades, and ASD is now a major public health burden. So far, only treatments to alleviate symptoms are available, with still unmet need for an effective disease treatment to reduce ASD core symptoms. Genetic predisposition alone can only explain a small fraction of the ASD cases. It has been reported that environmental factors interacting with specific inter-individual genetic background may induce immune dysfunctions and contribute to the incidence of ASD. Such dysfunctions can be observed at the central level, with increased microglial cells and activation in ASD brains or in the peripheral blood, as reflected by high circulating levels of pro-inflammatory cytokines, abnormal activation of T-cell subsets, presence of auto-antibodies and of dysregulated microbiota profiles. Altogether, the dysfunction of immune processes may result from immunogenetically-determined inefficient immune responses against a given challenge followed by chronic inflammation and autoimmunity. In this context, immunomodulatory therapies might offer a valid therapeutic option. Mesenchymal stromal cells (MSC) immunoregulatory and immunosuppressive properties constitute a strong rationale for their use to improve ASD clinical symptoms. studies and pre-clinical models have shown that MSC can induce synapse formation and enhance synaptic function with consequent improvement of ASD-like symptoms in mice. In addition, two preliminary human trials based on the infusion of cord blood-derived MSC showed the safety and tolerability of the procedure in children with ASD and reported promising clinical improvement of core symptoms. We review herein the immune dysfunctions associated with ASD provided, the rationale for using MSC to treat patients with ASD and summarize the current available studies addressing this subject.
自闭症谱系障碍（ASD）是一组异质性神经发育疾病，其特征为社交互动受损和重复行为。在过去几十年中，报告的病例数量有所增加，ASD现已成为一项重大的公共卫生负担。到目前为止，仅有缓解症状的治疗方法，对于有效治疗疾病以减轻ASD核心症状的需求仍未得到满足。仅遗传易感性只能解释一小部分ASD病例。据报道，与特定个体遗传背景相互作用的环境因素可能会诱发免疫功能障碍，并导致ASD的发生。这种功能障碍可在中枢水平观察到，ASD大脑中的小胶质细胞增加并被激活，或者在外周血中也有体现，表现为促炎细胞因子循环水平升高、T细胞亚群异常激活、自身抗体的存在以及微生物群谱失调。总之，免疫过程的功能障碍可能是由于免疫遗传决定的针对特定挑战的免疫反应效率低下，随后引发慢性炎症和自身免疫。在这种情况下，免疫调节疗法可能提供一种有效的治疗选择。间充质基质细胞（MSC）的免疫调节和免疫抑制特性为其用于改善ASD临床症状提供了有力的理论依据。研究和临床前模型表明，MSC可以诱导突触形成并增强突触功能，从而改善小鼠的ASD样症状。此外，两项基于输注脐带血来源的MSC的初步人体试验显示了该程序在ASD儿童中的安全性和耐受性，并报告了核心症状有令人鼓舞的临床改善。我们在此回顾与ASD相关的免疫功能障碍，使用MSC治疗ASD患者的理论依据，并总结当前针对该主题的现有研究。
