CEPO基因转染hUCMSCs对宫内感染致新生大鼠脑白质损伤的作用研究

In recent years, human umbilical cord derived mesenchymal stem cells (hUCMSCs) have caused increasing interest as candidates of transplantation to repair damage in the central nervous system of infants, and the underlying mechanisms of these findings remain unclear.On the other hand,limits of hUCMSCs have hindered its application.Carbamylated erythropoietin(CEPO) is derivant of EPO,which has no ability of producing red blood cells but has powerful impact on protecting nervous damage.We have previously demonstrated that CEPO could decrease apoptosis of hUCMSCs and promoted differentiation of hUCMSCs to nerve cells,at the same time, CEPO could regulate the expression of immune molecules on hUCMSCs.So it is possible that hUCMSCs can better repair brain damage after genetically modified by CEPO,and the mechanisms may involve regulating effect of hUCMSCs on Immune cells and cytokines. On the basis of preliminary work, we will study the therapeutic effects and mechanisms of hUCMSCs transfected by CEPO gene after transplantation in a neonatal rat model of white matter damage (WMD) in brain after intrauterine, and study the correlation about immunoregulation of CEPO-hUCMSCs and its protective effect on neonatal brain damage. This subject may supply scientific basis and strategy on clinical treatment of WMD in infants.

近年来脐带间充质干细胞（hUCMSCs）对新生动物脑损伤的作用备受关注，但作用机制仍不清楚，另外hUCMSCs自身的局限性也是其应用的瓶颈。氨基甲酰促红细胞生成素（CEPO）是EPO的衍生物，无促红细胞生成活性但具有强大的神经保护功能。我们在前期工作中发现CEPO可促进hUCMSCs向神经细胞分化，并调控hUCMSCs免疫分子的表达，因此，我们推测经过CEPO修饰的hUCMSCs可以更好的修复脑损伤，其作用机制可能涉及对新生鼠免疫细胞和细胞因子的调节。本课题以此为切入点，将CEPO基因转染到hUCMSCs中，观察CEPO的作用及信号通道；建立宫内感染致新生大鼠脑白质损伤模型，将转染细胞移植入大鼠脑组织，评估大鼠的学习记忆能力，另与模型鼠免疫细胞共培养，监测免疫细胞及细胞因子的变化，从免疫学的角度进一步研究CEPO-hUCMSCs对新生大鼠脑损伤的作用及相关机制，为今后临床应用提供科学依据。