Stem Cell Therapy for HIE

HIE 的干细胞疗法

• 批准号: 7250793
• 负责人: MICHAEL D WEISS
• 金额: $ 19.23万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7250793
• 关键词: Affect; Animal Model; Animals; Apoptosis; Area; Asphyxia; Axon; Birth; Brain; Brain region; Cell division; Cells; Cerebral Palsy; Cerebral cortex; Cessation of life; Chemicals; Clinical; Cytolysis; Disabled Persons; Edema; Electron Microscopy; Environment; Epilepsy; Event; Exhibits; Hour; Hypoxia; Implant; Injury; Ischemic-Hypoxic Encephalopathy; Label; Learning Disabilities; Left; Location; Mental Retardation; Modeling; Mus; Necrosis; Neonatal; Neurologic; Neuronal Injury; Neurons; Phenotype; Physiological; Research; Secondary to; Stem cell transplant; Stem cells; Subependymal; Supportive care; Synapses; Testing; Transplantation; base; cell type; central nervous system injury; day; handicapping condition; injured; lateral ventricle; mouse model; neonatal hypoxic-ischemic brain injury; neonate; neuropsychological; pup; stem cell therapy; success

DESCRIPTION (provided by applicant): Hypoxic-Ischemic Encephalopathy (HIE) is the brain manifestation of systemic asphyxia which occurs in 20 out of 1000 births. 25% of neonates who suffer from HIE exhibit severe permanent neuropsychological handicaps in the form of cerebral palsy, with or without associated mental retardation, learning disabilities, or epilepsy. Due to the devastating consequences of HIE, much research has focused on interrupting the cascade of events which are triggered by HIE. In the lab, these therapies have shown mixed results in limiting neuronal injury when given before or after the hypoxic-ischemic insult. These therapies have met with even more limited success in the clinical environment and the clinician's main armamentarium still remains supportive care. Stem cell therapy offers an attractive therapy for HIE. The ability to replace necrotic cells with functional cells would potentially limit the degree of long term neurological deficits. This therapy is particularly suited to the neonate due to the continued division of cells in the subventricular zones of the developing brain. This division essentially leaves intact chemical and cellular sign posts for the implanted stem cells to migrate and differentiate. Based on the fertile milieu in the developing brain, we hypothesize that stem cells implanted into the ventricles of neonatal mouse pups following hypoxic-ischemic brain injury will migrate to the area of injury and differentiate. The proposed hypothesis will be tested by using a mouse model of HIE. Following injury, stem cells will be implanted into the injured animal in either the lateral ventricle or injured cortex at 24 hours and 7 days post injury. Brains will then be collected 7-14 days post transplant. The location, cell type, and degree of differentiation of the transplanted stem cells will be analyzed. Axonal tracing studies will also be performed to begin to understand the physiologic activity of the implanted cells. Hypoxic-Ischemic Encephalopathy (HIE) is the brain manifestation of systemic asphyxia which occurs in 20 out of 1000 births. 25% of neonates who suffer from HIE exhibit severe permanent neuropsychological handicaps in the form of cerebral palsy, with or without associated mental retardation, learning disabilities, or epilepsy. This project begins to explore a potential therapy, stem cell transplants, for HIE using an animal model.

描述（由申请人提供）：缺氧 - 缺血性脑病（HIE）是全身性窒息的大脑表现，发生在1000个出生中的20个中。患有HIE的新生儿中有25％表现出严重的永久性神经心理障碍，形式为脑瘫，有或没有相关的智力障碍，学习障碍或癫痫病。由于HIE的毁灭性后果，许多研究重点是中断HIE触发的一系列事件。在实验室中，这些疗法在缺氧 - 缺血性损伤之前或之后表现出限制神经元损伤的结果。这些疗法在临床环境中取得了更大的成功，而临床医生的主臂系仍然仍然是支持性护理。干细胞疗法为HIE提供了有吸引力的疗法。用功能细胞代替坏死细胞的能力可能会限制长期神经缺陷的程度。由于发育中大脑的室室内区域中细胞的持续分裂，这种疗法特别适合新生儿。该分裂本质上留下了完整的化学和细胞符号柱，供植入的干细胞迁移和区分。基于发育中的大脑中肥沃的环境，我们假设在缺氧 - 缺血性脑损伤后植入新生小鼠幼崽心室的干细胞将迁移到损伤区域和区分。提出的假设将通过使用HIE的小鼠模型来检验。受伤后，在受伤后24小时零7天，干细胞将在受伤的动物中植入受伤的动物或受伤的皮质。然后，将在移植后7-14天收集大脑。将分析移植干细胞的位置，细胞类型和分化程度。还将进行轴突跟踪研究，以开始了解植入细胞的生理活性。缺氧 - 缺血性脑病（HIE）是全身性窒息的大脑表现，发生在1000个出生中的20分。患有HIE的新生儿中有25％表现出严重的永久性神经心理障碍，形式为脑瘫，有或没有相关的智力障碍，学习障碍或癫痫病。该项目开始使用动物模型探索潜在的疗法，即干细胞移植。