嗅鞘细胞协同脂肪间充质干细胞促进电烧伤周围神经损伤再生作用及其机制研究

Peripheral nerve injury repair and functional reconstruction is a hot research topic in burn field. Schwann cells and Slit / Robo signaling play a pivotal role in the regeneration of peripheral nerve. After occurrence of electric burn, the number of Schwann cells gradually decreased, which further leads to a reduction in secretion of neurotrophic and bioactive factors. Therefore,it is important to replenish the amounts of schwann cells to nerve injury microenviorment to promote nerve tissue regeneration and repair. Adipose-derived stem cells which possess multipotential differntiation, has been widely used for tissue regeneration and repair. Our previous study showed that olfactory ensheathing cells can secrete a lot of neurotrophic/bioactive factors which can provides a favorable microenviroment to promote differentiation of Adipose-derived stem cells into neural cells. The aims of present project will systemmatically investigate differentiation of the fat-derived mesenchymal stem cells as seed cells to Schwann cells, to further analyse the induction microenvironment of olfactory ensheathing cells co-culture microenvironment for screening an efficient strategy. Concomitantly, cell transplantation into the rat sciatic nerve model of electrical burns was conducted, and functional recovery of the sciatic nerve was observed and assessed, as well as the number of nerve fibers, myelin thickness and axonal diameter. Eventually,the molecualr mechanisms underlying differentiation of fat-derived mesenchymal stem cells into Schwann cells through Slit/Robo signaling will be further elucidated. The project may provid a noval solution to clinical therapy and repair of peripheral nerve injury in electrical burns by means of a combination of autologous transplantation of olfactory ensheathing cells and mesenchymal stem cells.

电烧伤周围神经损伤修复及功能重建的研究是组织修复的重点与难点。雪旺氏细胞和轴突生长导向分子Slit/Robo在周围神经再生中起关键作用。电烧伤周围神经损伤引起雪旺氏细胞缺失致营养因子分泌减少等诸多问题严重阻碍神经损伤后的修复，由于自体雪旺细胞来源缺乏，因而移植外源的雪旺氏细胞维持神经组织的存活、促进神经修复的微环境就显得尤为重要。近年来具有多向分化潜能的脂肪间充质干细胞，已成为组织修复广泛应用的种子细胞。我们前期研究发现：嗅鞘细胞可促使间充质干细胞分化成神经细胞，并为其分化提供了有利的微环境。本课题拟以脂肪间充质干细胞为切入点，通过与嗅鞘细胞共培养深入探讨诱导其共培养的微环境主要成分，检测诱导分化效率，筛选合适的细胞比例移植于大鼠坐骨神经电烧伤的模型，观察神经功能的恢复、神经纤维数目、髓鞘的厚度及轴索直径；进一步阐明导向分子Slit/Robo的调控机制，为电烧伤神经损伤提供新的治疗手段。

电烧伤周围神经损伤修复及功能重建的研究是组织修复的重点与难点。雪旺氏细胞和轴突生长导向分子Slit/Robo在周围神经再生中起关键作用。电烧伤周围神经损伤引起雪旺氏细胞缺失致使营养因子分泌减少等诸多问题严重阻碍了神经损伤和修复，因而移植大量的雪旺氏细胞来维持神经组织的存活、促进神经修复的微环境就显得尤为重要。近年来研究发现脂肪间充质干细胞具有多向分化潜能，因此已成为组织修复广泛应用的种子细胞。我们前期研究发现：嗅鞘细胞可促使间充质干细胞分化成神经细胞，并为其分化提供了有利的微环境。本课题拟以脂肪间充质干细胞为切入点，通过与嗅鞘细胞共培养深入探讨诱导其共培养的微环境主要成分，检测诱导分化效率，筛选合适的细胞比例移植于大鼠坐骨神经电烧伤的模型，观察坐骨神经功能的恢复、神经纤维数目、髓鞘的厚度及轴索直径；进一步阐明导向分子Slit/Robo信号通路的调控机制，为电烧伤神经损伤提供新的治疗手段。