Schwann cell repair of cauda equina ventral roots

描述（由申请人提供）：马尾由脊髓尾端产生的腹侧和背侧神经根集合形成。大约15-30%的脊柱创伤性损伤发生在胸腰段交界处或下方。因此，目前约有40，000名美国人遭受马尾神经损伤的衰弱影响。目标.这项研究的最终目标是在大鼠模型中识别和修复受损的腹根，作为概念验证，类似的技术可以可行地用于人类患者，因为没有治疗方法。这种潜在的转化应用形成了本研究的基础，因此，所有技术都符合临床实际限制。损伤模型和结果。为了实现这些目标，一种新的损伤模型已经在大鼠中开发，其中通过每个根的神经支配模式的电生理映射来识别腹根。在从这些根部切除短节段后，将通过26周跨度内的功能和行为结果来严格表征损伤对照，此时将分析再生的解剖学测量。以相同方式评估修复动物的再生。用雪旺细胞修复。鉴于其在周围神经修复中的再生作用，雪旺细胞被确定为腹根损伤后干预的理想候选者。改善的功能结果是主要的结果指标，尽管本研究比较了从不同部位采集的雪旺细胞的治疗，因为我们假设从前根采集的雪旺细胞（主要是运动表型）与从背根采集的雪旺细胞（主要是感觉表型）或坐骨神经采集的雪旺细胞（混合表型）相比，将显示出上级再生效果。作为体内测量的功能结果的前体，一系列体外实验将通过多重蛋白捕获的方式测量生长因子表达，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潜能。据推测，这种差异将在未来告知许旺细胞收获实践，理想情况下，通过从损伤部位适当的组织中提取的细胞的模态样扩增。 公共卫生相关性：马尾神经损伤与患者的衰弱后果有关，不幸的是，它在脊柱创伤性损伤后很常见。然而，不存在良好的损伤模型，并且目前的治疗方法严重缺乏。本研究的目的是：1）在一种新的损伤模型中使用雪旺细胞修复马尾神经前根，2）建立理想的雪旺细胞表型。

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. PUBLIC HEALTH RELEVANCE: Cauda equina injury is associated with debilitating consequences for patients, and it is unfortunately common following traumatic injury to the spine. However, no good injury models exist, and current treatments are severely lacking. This research aims to 1) repair cauda equina ventral roots in a novel injury model using Schwann cells and 2) establish the ideal Schwann cell phenotype for doing so.