CELLULAR THERAPY IN CHRONIC SPINAL CORD INJURY

长期目标是改善残余功能， 慢性脊髓损伤（SCI）区域的神经系统再生 我们建议使用迈阿密酒店的设施 治愈瘫痪项目发起了一个八部分的攻击， 难以解决的临床问题。 因为最近的研究表明，中枢神经元有能力 如果提供了一个改变的细胞环境， 提供细胞环境有益于 SCI区域的再生。 为了合理地发展这种方法， 对于人类SCI，我们必须首先记录各种类型的 为了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学， 人类脊髓损伤，并了解这种病理学如何与图像相关 用现代成像技术如磁共振成像 （项目2）。 对受伤者生理的更精确理解 用现代临床电生理技术测定人脐带， 在设计治疗方法时也是必要的（项目3）。 只 在这种背景下，我们可以在动物中选择合适的病变， 成功地模拟了人类病变的各个方面。 考虑如何 人类脊髓损伤的细胞环境可能会改变， 几个问题的答案。 细胞的潜在来源是什么 移植材料;是否可能和/或有必要使用 细胞系（项目4）？ 体外研究能否模拟体内条件， 从而定义了细胞相互作用，这些相互作用可能是允许的或抑制的， 再生反应（项目4）？ 人体组织遵循规则吗 来自再生反应的动物研究（项目4）？ 如何 免疫排斥反应在移植中发挥重要作用 SCI战略？ 设计了合适的病变模型， 有前途的细胞结构，我们必须评估两者的后果 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 然后将能够评估长期功能影响， 设计用于影响髓鞘形成状态的细胞移植， 新的纤维生长 我们强调许旺细胞的可能用途， 设计细胞植入物，因为使用这种细胞类型将使其 可以使用患者自身的组织来促进CNS再生。 这六个项目中提出的工作将得到核心方案的支持。 给药、组织学/电子显微镜检查、动物设施 护理/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.