Demyelination is a proper syndrome in plenty of central nervous system (CNS) diseases, which is the main obstacle to recovery and still lacks an effective treatment. To overcome the limitations of the brain-blood barrier on drug permeability, we modified an exosome secreted by neural stem cells (NSCs), which had transfected with lentivirus armed with platelet-derived growth factors A (PDGFA)-ligand. Through the and exosomes targeting test, the migration ability to the lesion areas and OPCs significantly improved after ligand modification. Furthermore, the targeted exosomes loaded with 3,5, 30-L-triiodothyronine (T3) have a critical myelination ability in CNS development, administrated to the cuprizone animal model treatment. The data shows that the novel drug vector loaded with T3 significantly promotes remyelination compared with T3 alone. At the same time, it improved the CNS microenvironment by reducing astrogliosis, inhibiting pro-inflammatory microglia, and alleviating axon damage. This investigation provides a straightforward strategy to produce a targeting exosome and indicates a possible therapeutic manner for demyelinating disease.

中文翻译：

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工程化 PDGFA 配体修饰的外泌体递送 T3 用于脱髓鞘疾病靶向治疗

脱髓鞘是多种中枢神经系统疾病的特有综合征，是康复的主要障碍，目前仍缺乏有效的治疗方法。为了克服脑血屏障对药物渗透性的限制，我们修饰了神经干细胞（NSC）分泌的外泌体，该外泌体已用携带血小板衍生生长因子 A（PDGFA）配体的慢病毒转染。通过外泌体靶向测试，配体修饰后向病变区域和OPCs的迁移能力显着提高。此外，负载有3,5,30-L-三碘甲状腺原氨酸（T3）的靶向外泌体在中枢神经系统发育中具有关键的髓鞘形成能力，用于铜宗动物模型治疗。数据显示，与单独的T3相比，负载T3的新型药物载体显着促进髓鞘再生。同时，它通过减少星形胶质细胞增生、抑制促炎性小胶质细胞和减轻轴突损伤来改善中枢神经系统微环境。这项研究提供了一种产生靶向外泌体的简单策略，并指出了脱髓鞘疾病的可能治疗方式。