DEVELOPMENT OF NEURAL CELL LINES FOR TRANSPLANTATION

用于移植的神经细胞系的开发

• 批准号: 3882480
• 负责人: MARY F D NOTTER
• 金额: --
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3882480
• 关键词: Ceboidea; Parkinson's disease; adrenal medulla; disease /disorder model; dopamine; glia; human tissue; hybrid cells; laboratory rat; model design /development; nervous system transplantation; neurons; substantia nigra; sympathetic nervous system; tissue /cell culture

The primary goal of this research is to obtain well defined, alternate sources of neural tissue for brain implantation to remedy central nervous system disorders such as Parkinson's disease. Three sources of neuronal cells will be examined and modulated in vitro to establish the potential of these cells for integration and stability within the host brain. (i) Established neuronal cell lines will be differentiated in vitro with antimitotic agents, vitamin A analogs and growth modulators and studied for cell surface properties and cell cycle kinetics. (ii) Dopaminergic neuronal cell hybrids will be produced by cell fusion of mitotic glial cells with embryonic substantia nigra cells to establish long- term, continuous, cultures of central dopamine neurons. These cells will also be screened for cell surface properties which are important criteria for potential integration within brain parenchyma. (iii) In addition, human and monkey adrenal medulla will be obtained from organ donation and cultured in vitro with growth factors and cocultured with cells which produce growth factors. Long-term cultures will be characterized for neuronal properties, the expression of transplantation antigens and colocalization of neuropeptides in this potentially transplantable tissue. Results of these studies will make available neural cells tailored for transplantation into primates with optimal characteristics and will lay the groundwork for repair of human CNS neurodegenerative diseases such as Parkinson's disease.

本研究的主要目标是获得定义明确， 脑移植的替代神经组织来源， 治疗中枢神经系统疾病，如帕金森氏症 疾病 将检查三种神经元细胞来源， 在体外调节，以建立这些细胞的潜力， 在宿主大脑中的整合和稳定性。 (i)建立 神经元细胞系将在体外用抗有丝分裂剂 药物、维生素A类似物和生长调节剂，并研究 细胞表面性质和细胞周期动力学。 (ii)多巴胺能 神经元细胞杂种将通过有丝分裂的细胞融合产生。 神经胶质细胞与胚胎黑质细胞建立长- 长期连续培养的中枢多巴胺神经元。 这些 还将筛选细胞的细胞表面性质， 脑内潜在整合的重要标准 薄壁组织 (iii)此外，人和猴的肾上腺髓质 将从器官捐赠中获得，并在体外培养， 生长因子并与产生生长的细胞共培养 因素 长期培养将表征神经元 特性、移植抗原的表达以及 神经肽在这个潜在的可移植的 组织. 这些研究的结果将使定制的神经细胞 用于移植到具有最佳特征的灵长类动物中， 将为人类中枢神经系统的修复奠定基础 神经退行性疾病，如帕金森病。