[F-18]DPA-714 PET/CT对放射性脑损伤的Muse细胞再生治疗效果评估的研究

Radiation-induced brain injury is one of the severe complications of radiotherapy for the intracranial tumor and cerebrovascular malformation. Due to the lack of diagnostic tools, limited clinical therapy methods and absence of effective medications, radiation-induced brain injury is often irreversible and has a poor prognosis. Finding an effective treatment strategy would be a crucial project to treat this lethal injury. Our previous study indicated that [F-18]DPA-714 PET/CT can detect the response of neuroinflammation at the early stage of brain injury. In addition, stem cells have a strong ability for neuranagenesis and immunomodulation. The aims of the study include: 1) Investigate the mechanism of radiation-induced nervous system injury and the neuroprotective effect of Muse cells by using BBB Kit model. 2) Evaluate the radiation-induced brain injury by [F-18]DPA-714 PET/CT. And investigate the immunomodulatory effect of Muse cell transplantation therapy. 3) Explore the nerve repair mechanism of Muse cells. And expand the understanding of the relationship between Muse cells and nervous system during the process of radiation-induced brain injury. This study will provide a new strategy for the diagnosis and treatment of radiation-induced brain injury.

迄今为止，放射性脑损伤的治疗仍缺乏有效手段。如何在保持高放射剂量的同时寻求一种安全高效的治疗策略，是当今中枢神经系统放射治疗的一项重要课题。我们在前期工作中发现，通过使用新型PET示踪剂[F-18]DPA-714，可在脑损伤早期即发现脑内的炎症变化。同时，干细胞极强的再生和对神经炎症的调节能力可抑制损伤的扩大并促进细胞的修复。本研究拟通过1）利用BBB Kit模型，模拟体外神经血管单元，探寻电离辐射对神经系统的损伤机制和Muse细胞的神经保护作用；2）利用[F-18]DPA-714 PET/CT影像技术进行放射性脑损伤的诊断并评估Muse细胞移植后对脑组织炎性变化的抑制作用；3）探索Muse细胞启动神经修复及神经保护的分子机制，拓展对放射性脑损伤过程中Muse细胞与神经系统间相互作用的认识。为放射性脑损伤诊治提供新策略。

放射治疗是治疗中枢神经系统（CNS）肿瘤和脑血管畸形的主要手段之一。但随之而来的放射性脑损伤问题也局限着此种治疗方法的发展。目前，以干细胞为主的靶向药物已受到广泛关注。间充质干细胞中的亚型多系分化持续应激（Muse）细胞即是最有潜力的细胞药物之一。本项目从神经再生医学及核医学领域出发，通过利用体外模型，确认了电离辐射对神经系统的损伤机制，并且通过对Muse细胞应用时间的把控，探索出其作为神经保护药物的最佳使用场景和时机。同时，新型[F-18]DPA-714 PET/CT影像技术的应用，明确了放射线照射对脑组织的影响，并显示出脑内损伤的炎症变化。我们的研究结果，证实了放射线照射及Muse细胞的神经保护间相互作用，该实验结果通过利用核医学成像和干细胞再生技术为放射性脑损伤的诊治开辟新策略。

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