触液神经元的神经干细胞潜能及其在脊髓损伤修复中作用研究

Spinal cord injury is currently a chronic incurable disease with a high incidence. Currently, there are no effective therapeutic strategies for spinal cord injury. The discovery of resident neural stem cells in the adult mammalian spinal cord has fueled interest in the development of regenerative therapies based on the recruitment of endogenous stem cells. The application of endogenous neural stem cells to repair spinal cord injury has become a research hotspot. However, the identity of adult neural stem cells remains controversial. Recently, Our data show that the cerebrospinal fluid-contacting neurons (CSF-CNs) express stem cell markers after spinal cord injury. Moreover, neurosphere forming assay demonstrated that CSF-CNs generated more neurospheres and expressed neural stem cell markers in vitro. In view of several studies indicating that CSF-CNs in adult have been shown to express doublecortin and Nkx6.1, two markers of juvenile neurons along with the neuron-specific nuclear protein typically expressed in mature neurons. They were suggested to remain in a rather incomplete maturation state. Thus, despite a pursuit of neuronal maturation during the postnatal period, CSF-CNs retain a durable low differentiated state. Altogether, there is the need, especially in mammals, for further studies to understand their physiological role in the central nervous system. Therefore, we proposed the hypothesis that "CSF-CNs have the potential of neural stem cells to participate in the repair of spinal cord injury ". This project intends to study the characteristics of neural stem cells of CSF-CNs and their proliferation and migration abilities in mouse model of spinal cord injury; In vitro, the CSF-CNs will be isolated from the periventricular area of the adult mammalian spinal cord for demonstration their multipotency through their production of neurons, astrocytes and oligodendrocytes. After the neurospheres of CSF-CNs infected with PKD2L1 promoter multimodality imaging molecular virus transplanted into injury site of spinal cord injury, we will observe whether they were involved in the repair of spinal cord injury by living animal imaging techniques. Through the injection of VEGF+bFGF into the lateral ventricle, the damaged CSF-CNs were targeted to verify the involvement of CSF-CNs in the repair of spinal cord injury. On the basis of the results of our study, we are expected to reveal the regenerative potential of CSF-CNs and explore its role to promote spinal cord repair following spinal cord injury. Moreover, this project aims to provide novel sources of neural stem cells for the clinical treatment of spinal cord injury.

脊髓损伤是一种高发生率、高致残性疾病，目前尚无有效治疗方法。神经干细胞为脊髓损伤的治愈带来了曙光，成年哺乳动物脊髓中存在内源性神经干细胞，应用其修复脊髓损伤具有独特优势，但是成体神经干细胞来源尚不清楚。我们发现脊髓损伤后触液神经元表达神经干细胞标记物，体外培养可形成神经球。其他文献报道触液神经元具有不成熟神经元特性。因此我们提出“触液神经元具有神经干细胞潜能，参与脊髓损伤修复”的假说。本项目以此为基础，体内检测触液神经元的干细胞标记物、增殖及迁移能力；体外通过触液神经元培养验证其自我更新及分化能力；通过触液神经元体内移植，VEGF+bFGF激活及靶向毁损触液神经元，在动物模型中验证触液神经元参与脊髓损伤修复。期望能够证明触液神经元具有神经干细胞潜能，在脊髓损伤修复中发挥作用。我们的研究为应用触液神经元治疗脊髓损伤提供实验基础，探索为临床治疗脊髓损伤提供新的神经干细胞来源。

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