Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by three core symptoms that include social interaction deficits, cognitive inflexibility, and communication disorders. They have been steadily increasing in children over the past several years, with no effective treatment. BTBR T+tf/J (BTBR) mice are an accepted model of evaluating autistic-like behaviors as they present all core symptoms of ASD. We have previously shown that transplantation of human bone marrow mesenchymal stem cells (MSC) to the lateral ventricles of BTBR mice results in long lasting improvement in their autistic behavioral phenotypes. Recent studies point exosomes as the main mediators of the therapeutic effect of MSC. Here, we tested whether treatment with the exosomes secreted from MSC (MSC-exo) will show similar beneficial effects. We found that intranasal administration of MSC-exo increased male to male social interaction and reduced repetitive behaviors. Moreover, the treatment led to increases of male to female ultrasonic vocalizations and significant improvement in maternal behaviors of pup retrieval. No negative symptoms were detected following MSC-exo intranasal treatments in BTBR or healthy C57BL mice. The marked beneficial effects of the exosomes in BTBR mice may translate to a novel, non-invasive, and therapeutic strategy to reduce the symptoms of ASD.

中文翻译：

---

鼻内施用源自间充质干细胞的外泌体可改善 BTBR 小鼠的自闭症样行为

自闭症谱系障碍 (ASD) 是一种神经发育障碍，以三个核心症状为特征，包括社交互动缺陷、认知僵化和沟通障碍。在过去的几年里，这种病在儿童中的发病率一直在稳步增加，但尚无有效的治疗方法。BTBR T+tf/J (BTBR) 小鼠是评估自闭症样行为的公认模型，因为它们表现出 ASD 的所有核心症状。我们之前已经证明，将人骨髓间充质干细胞（MSC）移植到 BTBR 小鼠的侧脑室可以长期改善其自闭症行为表型。最近的研究指出外泌体是 MSC 治疗效果的主要介质。在这里，我们测试了用 MSC 分泌的外泌体 (MSC-exo) 进行治疗是否会显示出类似的有益效果。我们发现鼻内施用 MSC-exo 可以增加男性之间的社交互动并减少重复行为。此外，该治疗导致雄性对雌性超声波发声的增加，以及母体取回幼崽的行为显着改善。对 BTBR 或健康 C57BL 小鼠进行 MSC-exo 鼻内治疗后，未检测到阴性症状。外泌体对 BTBR 小鼠的显着有益作用可能会转化为一种新颖的、非侵入性的治疗策略，以减轻 ASD 的症状。