Schwann cell repair of cauda equina ventral roots

马尾腹根的雪旺细胞修复

基本信息

批准号：
8395868
负责人：
Samuel John Mackenzie
金额：
$ 2.78万
依托单位：
UPSTATE MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-30 至 2013-05-27
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8395868
关键词：
Address Adult Afferent Neurons American Animals Area Axon Behavioral Biological Assay Bladder Brain-Derived Neurotrophic Factor Cauda Equina Cells Coculture Techniques Collection Control Groups Denervation Distal Dorsal Excision Exhibits Fibroblasts Foundations Future GDNF gene Genitourinary system Goals Growth Cones Growth Factor Harvest Human Implant In Vitro Inbred F344 Rats Individual Injury Intervention Intestines Laboratories Laminin Leg Life Location Maps Measures Mediating Modality Modeling Motor Motor Neurons Movement Muscle Myelin NTF3 gene Natural regeneration Nature Nerve Operative Surgical Procedures Organ Outcome Outcome Measure Paralysed Patients Pattern Peripheral Nerves Peripheral Nervous System Phenotype Physiological Plant Roots Proteins Rattus Recovery Research Schwann Cells Sensory Series Sexual Dysfunction Signal Transduction Site Spinal Spinal Cord Spinal Ganglia Spinal cord injury Stimulus Surgical sutures Symptoms Tail Techniques Testing Time Tissues Trauma Ventral Roots Vertebral column base functional outcomes gastrointestinal system improved improved functioning in vivo in vivo Model injured innovation interest nerve supply novel pleiotrophin primary outcome pup regenerative remyelination repaired research study sciatic nerve spinal nerve posterior root

项目摘要

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.

描述（由申请人提供）：Cauda Equina是由由脊髓的尾端产生的腹神经和背神经根的收集形成的。大约15-30％的脊柱创伤性伤害发生在胸甲交界处或下方。结果，目前约有40,000名美国人遭受了Cauda Equina受伤的衰弱影响。目标。这项研究的最终目标是在大鼠模型中识别和修复受伤的腹根，作为概念证明，即可以在不存在治疗的人类患者中使用类似的技术。这种潜在的翻译应用构成了这项研究的基础，因此，所有技术都遵循临床实际的约束。伤害模型和结果。为了达到这些目的，在大鼠中开发了一种新型的损伤模型，在大鼠中，通过对每个根的神经支配模式的电生理图鉴定腹根。从这些根部切除短段后，将通过在26周的跨度内通过功能和行为结果来严格表征受伤的控制，这将分析再生的解剖学测量。修复动物的再生将以相同的方式进行评估。用雪旺细胞修复。鉴于它们在周围神经修复中有记录的再生作用，因此将雪旺细胞确定为腹侧根部损伤后干预的理想候选者。改善功能结果是感兴趣的主要结果度量，尽管这项研究将治疗与从不同位点收获的雪旺细胞进行了比较，因为我们假设从腹部根部收获的那些（主要是运动表型）将显示出与从背部（主要是感觉现象）或Sciat sciat神经（混合现象）（混合现象）相比，将显示出优质的再生作用。作为在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每个细胞组的再生效力。假设这种差异将来将为Schwann细胞收集实践提供信息，理想情况下是通过适当的损伤部位从组织中采取的细胞的模态膨胀。