TLR3配体预处理骨髓间充质干细胞对其治疗帕金森病的影响及机制研究

Bone marrow mesenchymal stem cells (BM-MSCs) are potential promising cells to treat Parkinson`s disease (PD). It is an urgent need to enhance their migration without affecting their immunosuppressive ability. The activated Toll-like receptors (TLRs), especially TLR3, could facilitate cell migration, but the effects of activated MSCs on PD are still unknown. In this study, we will investigate the TLRs expression in rat bone marrow mesenchymal stem cells (rBM-MSCs), and then observe their effects on the migration and immunosuppressive ability of rBM-MSCs. The effects of TLR3 on the related biological properties and functions of rBM-MSCs will be explored. We will clarify the pathway through which TLR3 works. Finally, we will evaluate the therapeutic effects of TLR3 activated rBM-MSCs on Parkinsonian mice via CSF delivery, investigate the underlying mechanisms and trace the distribution of rBM-MSCs in the brain of PD mice. In this study, we will uncover the TLRs in rBM-MSCs, and reveal the TLR3 effects on rBM-MSCs treating PD, for providing a new way to treat PD.

骨髓间充质干细胞（BM-MSCs）对治疗帕金森病（PD）有很大的应用潜能，如何提高细胞迁移能力又不影响其免疫抑制能力是需要解决的重要问题之一。新近研究发现Toll样受体（尤其是TLR3）的活化能够促进细胞迁移，但活化后的细胞对PD的疗效尚不明确。本研究首先检测TLRs各亚型在大鼠BM-MSCs（rBM-MSCs）中的表达情况，观察其相应配体对BM-MSCs迁移能力和免疫抑制能力的影响。接下来探索TLR3对BM-MSCs的生物学特性和相关功能的影响，并阐明MAPK和NF-κB通路在其中发挥的作用。最后将TLR3配体预处理的rBM-MSCs输注到PD小鼠脑脊液中，评价其疗效并探讨相关机制。本课题将全面的揭示TLRs受体在rBM-MSCs中的表达情况及相关功能，系统的研究TLR3配体对rBM-MSCs功能的影响及机制并为PD的治疗提供新方法。