Role of NG2+ glial cells in recovery from spinal cord injury

 描述（由申请人提供）：美国约有5，596，000人患有某种形式的瘫痪;其中，1，275，000人因脊髓损伤（SCI）而瘫痪。缺乏治疗导致人口不断增长。每年，SCI给医疗保健系统带来的成本约为405亿美元。SCI引发神经胶质细胞行为的深刻变化，这限制了继发性损伤并影响再生。然而，不同类型的胶质细胞在SCI恢复中的不同作用还不清楚。NG2+ 神经胶质细胞是一类在发育和成年CNS中产生少突胶质细胞的神经胶质祖细胞，在SCI后迅速动员;它们增加增殖并迁移到损伤部位。 伤害。这种NG 2+细胞募集的后果尚不清楚。尽管这些细胞的行为主要是在少突胶质细胞再生的背景下观察的，但最近的研究表明它们可能在SCI的病理生理学中发挥额外的作用。在这项探索性研究资助（R21）中，我们建议在临床相关的挫伤诱导SCI模型中，使用体内遗传谱系追踪、体内双光子成像和体内选择性细胞消融来检查这些高度动态细胞的命运，并评估它们对功能恢复的贡献。从这些研究中获得的知识可以揭示基于操纵这种内源性祖细胞库以及靶向操纵NG 2+细胞（也称为工程化用于移植治疗的少突胶质细胞前体细胞（OPC））的新的治疗策略。

 DESCRIPTION (provided by applicant): Approximately 5,596,000 people in the United States live with some form of paralysis; among these, 1,275,000 are paralyzed as the result of a spinal cord injury (SCI). The lack of treatment results in a constantly growing population. Each year, SCI cost to the health care system is roughly 40.5 billion. SCI triggers profound changes in the behavior of glial cells, which limit secondary injury and influence regeneration. However, the distinct roles of different glial cell types in the recovery from SCI are not well understood. NG2+ glial cells, a class of glial progenitors that generate oligodendrocytes in the developing and adul CNS, are rapidly mobilized following SCI; they increase their proliferation and migrate to the site of injury. The consequences of this recruitment of NG2+ cells are unknown. Although the behavior of these cells has been viewed primarily in the context of oligodendrocyte regeneration, recent studies suggest that they may play additional roles in the pathophysiology of SCI. In this exploratory research grant (R21) we propose to examine the fate of these highly dynamic cells and evaluate their contribution to functional recovery using in vivo genetic lineage tracing, in vivo two photon imaging, and in vivo selective cell ablation in a clinically relevant model of contusion-induced SCI. The knowledge gained from these studies may reveal new therapeutic strategies based on manipulation of this endogenous pool of progenitors as well as targeted manipulation of NG2+ cells (also termed oligodendrocyte precursor cells (OPCs) engineered for transplantation therapy.