CELLULAR THERAPY IN CHRONIC SPINAL CORD INJURY

长期目标是改善剩余功能并促使中央 慢性脊髓损伤(SCI)区域的神经系统再生 在人类身上。我们建议使用迈阿密的广泛设施 治疗瘫痪项目对此发起八部分攻击 临床难题和悬而未决的问题。 因为最近的研究表明中枢神经元有能力 再生如果提供了改变的蜂窝环境，我们将寻求 提供有益的蜂窝环境的具体方式 脊髓损伤区域的再生。要合理地开发这种方法，以 人类脊髓损伤后，首先要记录临床病程 人类的伤害，以便更好地预测最终结果(项目 1)。我们还必须更好地了解各种疾病的病理 人类脊髓损伤，并了解这种病理与图像的相关性 通过现代成像技术获得的，例如磁共振成像 (项目2)。对伤者的生理有更准确的了解 用现代临床电生理技术检测的人脐带 在设计治疗方法时也是必要的(项目3)。仅限 在这种背景下，我们能否在动物身上选择合适的病变 成功地模仿了人体损伤的各个方面。思考如何将 人脊髓损伤的细胞环境可能需要改变 几个问题的答案。细胞的潜在来源是什么？ 移植材料；是否有可能和/或有必要使用 细胞系(项目4)？体外研究可以模拟体内条件和 从而定义可能允许或抑制的细胞相互作用 再生反应(项目4)？人体组织遵守规则吗？ 来自动物再生反应的研究(项目4)？多么 免疫排斥在移植中的重要作用 SCI中的策略？ 设计合适的损伤模型并进行设计和移植 有希望的细胞结构，我们必须评估对两者的后果 感觉和运动系统。这将需要更好地定义选定的 大鼠脊髓的感觉和运动机制(项目5和6)。我们 将能够评估长期的功能影响 细胞移植旨在影响髓鞘形成和 新的纤维生长。我们强调施万氏细胞在 设计细胞植入物，因为使用这种细胞类型将使 可能使用患者自己的组织来促进中枢神经系统的再生。 这六个项目中提议的工作将由Core提供支持 管理设施、组织学/电子显微镜、动物 关怀/行为测试和统计。

The long-term goal is to improve residual function and to prompt central nervous system regeneration in regions of chronic spinal cord injury (SCI) in man. We propose to use the broad scope of the facilities of The Miami Project to Cure Paralysis to initiate an eight part attack on this difficult and unresolved clinical problem. Because recent research has shown that central neurons have the capacity to regenerate if provided with an altered cellular environment we will seek specific ways in which to provide a cellular environment salutary for regeneration in regions of SCI. To rationally develop this approach for human SCI we must first document the clinical course after various types of injury in the human in order to better predict eventual outcome (Project 1). We must also better understand the pathology of the various kinds of human cord injury, and learn how this pathology correlates with images obtained with modern imaging techniques, such as magnetic resonance imaging (Project 2). A more precise understanding of the physiology of the injured human cord as assayed with modern clinical electrophysiologic techniques is also necessary in devising therapeutic approaches (Project 3). Only against this background can we select suitable lesions in animals that successfully mimic aspects of the human lesion. Consideration of how the cellular environment of the human cord injury might be altered requires answers to several questions. What are the potential sources of cellular material for transplantation; will it be possible and/or necessary to use cell lines (Project 4)? Can in vitro studies mimic in vivo conditions and thus define cellular interactions that may be permissive or inhibitory for a regenerative response (Project 4)? Do human tissues follow the rules derived from animal studies in regenerative responses (Project 4)? How important a role will immunological rejection play in transplantation strategies in SCI? Having devised suitable lesion models and designed and transplanted promising cellular constructs, we must assess the consequences on both sensory and motor systems. This will require better definition of selected sensory and motor mechanisms in the rat spinal cord (Projects 5 and 6). We will then be in a position to assess the long-term functional effects of cellular transplants designed to influence the status of myelination and new fiber growth. We emphasize the possible use of the Schwann cell in designing cellular implants because use of this cell type would make it possible to use the patient's own tissues to facilitate CNS regeneration. The work proposed in these six projects will be supported by Core facilities for Administration, Histology/Electron Microscopy, Animal Care/Behavioral Testing, and Statistics.