SynCAM1基因修饰EMSCs联合纤维蛋白支架移植促进脊髓损伤修复的机制研究

Although stem cell transplantation is regarded as one of the most promising treatments to repair the injured spinal cord, there are still some problems to be solved at present, such as: (1) how to obtain a sufficient number of seed cells for autologous transplantation? (2) how to promote synapse formation and construct relay circuits between transplanted cells and host neurons? It is known that SynCAM1 is localized on pre- and post-synaptic terminals of neurons and functions as a homophilic adhesion molecule that spans the synaptic cleft. In our earlier study, we found that fibrin scaffolds containing ectomesenchymal stem cells (EMSCs) can enhance behavioral and histological improvement in a rat model of spinal cord injury，and it plays an important role in the differentiation of neural stem cells for lipid raft orchestrate. We hereby hypothesize that SynCAM1 forms a homologous dimer between adjacent nerve cells, and recruits synapse formation related proteins to form lipid rafts to promote the formation of synapses. In order to explore the mechanism of how SynCAM1 affect synaptic connection among EMSCs, co-culture systems will be constructed between SynCAM1-overexpressed EMSCs and fibrin glue in vitro. Meanwhile, SynCAM1-overexpressed EMSCs and fibrin glue were co-implanted into the spinal cord injury site of rats to evaluate the recovery of hind limb motor function in rats. The outcomes will reveal the important role of SynCAM1 gene in cell transplantation and provide a new strategy for cell transplantation to repair the spinal cord injury.

干细胞移植是修复脊髓损伤最有应用前景的治疗手段之一。但是，如何获得足够可供自体移植的种子细胞、如何促进移植细胞之间形成突触依然是亟待解决的难题。SynCAM1同时分布于突触前膜和后膜，具有嗜同源黏附的特性，介导细胞间突触的连接。我们前期研究发现大鼠外胚间充质干细胞（EMSCs）与纤维蛋白支架共移植可有效治疗脊髓损伤;脂筏结构在神经干细胞的分化过程中起重要作用。因此我们提出假说:SynCAM1通过相邻神经细胞间形成同源二聚体，并募集突触形成的相关分子形成脂筏结构，促进突触形成。我们将SynCAM1高表达EMSCs与纤维蛋白支架共培养，探讨SynCAM1对EMSCs建立突触连接的作用机制。同时，将SynCAM1高表达的种子细胞与纤维蛋白支架共植到大鼠脊髓损伤部位，观察大鼠后肢运动功能的恢复情况。研究结果将揭示SynCAM1基因在细胞移植中的重要作用，为细胞移植修复脊髓损伤提供新策略。

干细胞移植是修复脊髓损伤最有应用前景的治疗手段之一。但是，如何获得足够可供自体移植的种子细胞、如何促进移植细胞之间形成突触依然是亟待解决的难题。SynCAM1同时分布于突触前膜和后膜，具有嗜同源黏附的特性，介导细胞间突触的连接。我们前期研究发现大鼠外胚间充质干细胞（EMSCs）与纤维蛋白支架共移植可有效治疗脊髓损伤；脂筏结构在神经干细胞的分化过程中起重要作用。因此我们提出假说：SynCAM1通过相邻神经细胞间形成同源二聚体，并募集突触形成的相关分子形成脂筏结构，促进突触形成。我们将SynCAM1高表达EMSCs与纤维蛋白支架共培养，探讨SynCAM1对EMSCs建立突触连接的作用机制。同时，将SynCAM1高表达的种子细胞与纤维蛋白支架共植到大鼠脊髓损伤部位，观察大鼠后肢运动功能的恢复情况。研究结果将揭示SynCAM1基因在细胞移植中的重要作用，为细胞移植修复脊髓损伤提供新策略。