Schwann cell repair of cauda equina ventral roots

描述（由申请人提供）：马尾是由脊髓尾端产生的腹侧和背侧神经根的集合形成的。大约15-30%的脊柱创伤发生在胸腰椎连接处或以下。因此，目前约有40,000名美国人遭受马尾损伤的衰弱影响。的目标。这项研究的最终目标是在大鼠模型中识别和修复受伤的腹侧神经根，以证明类似的技术在人类患者中是可行的，目前还没有治疗方法。这种潜在的转化应用构成了本研究的基础，因此，所有技术都坚持临床实践的限制。损伤模型和结果。为了达到这些目的，在大鼠中开发了一种新的损伤模型，其中通过对每个根的神经支配模式的电生理映射来识别腹侧根。从这些根上切除短节段后，受伤对照将在26周的时间内通过功能和行为结果严格表征，届时将分析再生的解剖学测量。修复动物的再生将以同样的方式进行评估。用雪旺细胞修复。鉴于其在周围神经修复中的再生作用，雪旺细胞被认为是腹根损伤后干预的理想候选者。虽然本研究比较了来自不同部位的雪旺细胞的治疗，但改善的功能结果是主要的结果衡量标准，因为我们假设来自腹根（主要是运动表型）的雪旺细胞比来自背根（主要是感觉表型）或坐骨神经（混合表型）的雪旺细胞表现出更好的再生效果。作为在体内测量功能结果的先驱，一系列的体外实验将通过多重蛋白捕获来测量生长因子的表达，并通过与运动或感觉神经元共培养来描绘每个细胞组的再生能力。据推测，这些差异将为未来的雪旺细胞采集实践提供信息，理想情况下，通过从损伤部位的组织中提取细胞进行模态样扩增。

DESCRIPTION (provided by applicant): The cauda equina is formed from collection of ventral and dorsal nerve roots arising from the caudal end of the spinal cord. Approximately 15-30% of traumatic injuries to the spine occur at or below the thoracolumbar junction. As a result, about 40,000 Americans currently suffer from the debilitating effects of cauda equina injury. Goal. This study's ultimate goal is to identify and repair injured ventral roots in a rat model as proof-of-concept that similar techniques could feasibly be used in human patients, for which no treatments exist. This potential translational application forms the foundation for this study, and as such, all techniques adhere to clinically practical constraints. Injury model and outcomes. To achieve these ends, a novel injury model has been developed in the rat where ventral roots are identified by way of electrophysiological mapping of each root's innervation pattern. Following excision of short segments from these roots, injured controls will be rigorously characterized by way of functional and behavioral outcomes over a 26-week span, at which point anatomical measures of regeneration will be analyzed. Regeneration in repaired animals will be assessed in the same manner. Repair with Schwann cells. Given their documented regenerative effect in peripheral nerve repair, Schwann cells were identified as ideal candidates for intervention following ventral root injury. Improved functional outcome is the primary outcome measure of interest, though this study compares treatment with Schwann cells harvested from different sites, as we hypothesize that those harvested from ventral roots (predominantly motor phenotype) will show superior regenerative effect compared to those harvested from dorsal roots (predominantly sensory phenotype) or sciatic nerves (mixed phenotypes). As a precursor to the functional outcomes measured in vivo, a series of in vitro experiments will measure growth factor expression by way of multiplex protein capture and delineate the regenerative potency of each cell group through co-culture with motor or sensory neurons. It is hypothesized that such differences will inform Schwann cell harvesting practices in the future, ideally through modality-like expansion of cells taken from tissue at the injury site proper.