NSC Function in a Motor Cortex TBI

运动皮层 TBI 中的 NSC 功能

• 批准号: 10089946
• 负责人: Franklin D West
• 金额: $ 39.05万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10089946
• 关键词: Address; Anatomy; Animals; Astrocytes; Biomechanics; Brain; Brain Injuries; Brain region; Cause of Death; Cell Therapy; Cell physiology; Child; Childhood; Confocal Microscopy; Development; Engraftment; Environment; Event; Family suidae; Foundations; Functional Magnetic Resonance Imaging; Future; Gait; Glial Fibrillary Acidic Protein; Human; In Vitro; Investigation; Knowledge; Lead; Learning; Length; Machine Learning; Magnetic Resonance Imaging; Measurable; Measures; Mediating; Memory; Modeling; Morphology; Motor; Motor Cortex; Neurites; Neurons; Oligodendroglia; Outcome; Patients; Pattern; Physiological; Physiology; Quality of life; Recovery of Function; Research; Rest; Rodent; Rodent Model; SOX1 gene; Signal Transduction; Stem cell transplant; Structure; Testing; Therapeutic; Tissue Engineering; Tissues; Transplantation; Traumatic Brain Injury; Tubulin; Weight; Work; association cortex; base; brain tissue; cell type; clinically relevant; cognitive function; disability; experience; functional outcomes; gray matter; improved; induced pluripotent stem cell; innovation; insight; motor deficit; motor function recovery; myelination; nerve injury; nerve stem cell; neural correlate; neural network; novel; pediatric traumatic brain injury; regenerative; relating to nervous system; repaired; stem cell biology; stem cell differentiation; stem cell fate; stem cell therapy; stroke model; stroke therapy; synaptogenesis; white matter

Project Summary Traumatic brain injury (TBI) is a leading cause of death and disability in children with 37,200 children suffering a severe TBI with most dying or experiencing “unfavorable outcomes” within 6 months. Neural stem cells (NSCs) have been seen as a potential therapeutic option for severe pediatric TBI with the ability to differentiate and integrate into TBI brain tissue and replace damaged and lost neural networks. Many of these studies have demonstrated that NSC therapy leads to significant improvements in motor function, learning and memory in rodent models. However, no study to date has closely examined the potential of NSC to undergo region specific differentiation in a discreate injured brain region and correlated it with a measurable change in brain network activity and functional recovery. In this application, we propose to fill this knowledge gap by examining in-depth the effect of transplanted NSC differentiation and engraftment into the damaged primary motor cortex on improving brain motor network activity and motor function in a pediatric piglet model. We hypothesize that induced pluripotent stem cell (iPSC) derived NSCs (iNSCs) transplanted into the damaged primary motor cortex will undergo region specific neural differentiation leading to brain motor network and motor function recovery in a pediatric piglet TBI model. The contribution of this work is highly significant and innovative since successful completion of this project will directly lead to new insights into the ability of transplanted iNSC to undergo regionalized specific differentiation and integration, and rigorously and quantitatively assess functional recovery at the brain and whole animal level. This critical information will advance TBI cell therapy with broad implications in the neural injury, cell therapy, and tissue engineering fields at large. Testing in a translational pig model is critical due to key similarities in brain anatomy and physiology relative to rodents; thus, making findings in the pig more predictive of what would occur in human patients.

项目摘要 创伤性脑损伤（TBI）是导致儿童死亡和残疾的主要原因，有37，200名儿童患有创伤性脑损伤。 严重TBI，大多数在6个月内死亡或经历“不利结果”。神经干细胞 已被视为严重儿童TBI的潜在治疗选择， 整合到TBI脑组织中并替换受损和丢失的神经网络。其中许多研究 NSC治疗导致运动功能，学习和记忆的显着改善， 啮齿动物模型。然而，迄今为止，还没有研究仔细研究过国家安全理事会进行区域具体评估的潜力。 分化的一个discreet受伤的大脑区域，并将其与脑网络的可测量的变化 活动和功能恢复。在本申请中，我们建议通过深入研究来填补这一知识空白 移植的NSC分化和植入到受损的初级运动皮层中对 改善小儿仔猪模型中的脑运动网络活动和运动功能。我们假设 将诱导多能干细胞（iPSC）衍生的NSC（iNSC）移植到受损的初级运动中 皮层将经历区域特异性神经分化，导致大脑运动网络和运动神经网络的形成。 在小儿仔猪TBI模型中的功能恢复。这项工作的贡献是非常重要的， 创新，因为这个项目的成功完成将直接导致新的见解的能力， 移植iNSC进行区域化的特异性分化和整合，并严格 定量评估脑和整个动物水平的功能恢复。这一重要信息将提前 TBI细胞治疗在神经损伤、细胞治疗和组织工程领域具有广泛的意义。 在平移猪模型中进行测试是至关重要的，这是因为相对于 因此，在猪身上的发现更能预测在人类患者身上会发生什么。