Characterizing marrow derived cells for neural therapy

表征用于神经治疗的骨髓来源细胞

• 批准号: 6934288
• 负责人: KENDRICK C BOARDMAN
• 金额: $ 10.11万
• 依托单位: NEOCYTEX BIOPHARMA, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934288
• 关键词: DNA methylation; aging; astrocytes; athymic mouse; biomarker; bone marrow; bromodeoxyuridine; carcinogenesis; cell differentiation; cell line; cell migration; cell population study; cell transplantation; cytogenetics; flow cytometry; hematopoietic stem cells; human tissue; immunocytochemistry; immunogenetics; karyotype; mixed tissue /cell culture; nervous system regeneration; neural degeneration; neurogenesis; neurons; oligodendroglia; therapy design /development

DESCRIPTION (provided by applicant): Neurodegenerative diseases and injuries of the central nervous system (CMS) - such as Alzheimer's disease, Parkinson's desease, amytrophic leteral sclerosis (ALS), and stroke - disable and kill millions of American's each year, yet there is no cure or even effective treatment for any of these diseases. The discovery of multipotent neural stem cells (NSCs) in adult brain has brought about revolutionary changes in the theory of neurogenesis; however, therapies being developed from embryonic stem cells and NSCs directly isolated from brains are fraught with a number of technical (tumor-/teratoma- genesis, uncontrolled multipotency, sourcing, require immune suppression) and ethical hurdles which have hindered rapid progress toward human therapy. This proposal builds upon the innovative discovery that bone marrow-derived cells (MDCs) cultured in the presence of a specific chemical agent leads to the generation of ACT-N(tm) cells that are capable of migrating and differentiating into new neural and glial cells when implanted into the lateral ventricle of rodent brains. Our long-term goal is to develop ACT-N cells as an effective therapy for patients with debilitating conditions of the CNS including, but not limited to, stroke, Alzheimer's disease, Parkinson's disease, and age-related memory impairment. To achieve this goal, we need to explore the potential ability of ACT-N cells to replace and/or augment the native repair mechanisms that are activated in CNS during disease and/or injury and also to develop robust and reproducible manufacturing strategies with the necessary safety, quality, and process controls. In regards to the latter need, this research plan intends to identify unique characteristics of ACT-N cells that differ from the MDCs from which they are derived, including immunophenotype, DNA methylation levels, and differentiation potential. In addition, initial considerations pertaining to ACT-N safety will be addressed.

描述（由申请人提供）：中枢神经系统（CMS）的神经退行性疾病和损伤 - 例如阿尔茨海默氏病，帕金森氏症，帕金森氏症，疗程疗程疗法（ALS）和中风（ALS）和中风 - 每年都禁用和杀死数百万美国人的治疗方法，但均无治愈的治疗方法，甚至有效地治疗了这些疾病。成人大脑中多能神经干细胞（NSC）的发现引起了神经发生理论的革命性变化。然而，由胚胎干细胞和直接从大脑分离的NSC开发的疗法充满了许多技术（肿瘤/畸胎瘤，不受控制的多能力，采购，需要免疫抑制）和伦理障碍，这些障碍阻碍了人类治疗的迅速发展。该提案建立在创新的发现上：在存在特定化学剂的存在下培养的骨髓衍生细胞（MDC）会导致植入啮齿动物大脑外侧的ACT-N（TM）细胞的产生，这些ACT-N（TM）细胞能够迁移并区分新的神经和神经胶质细胞。我们的长期目标是针对中枢神经系统疾病衰弱的患者开发ACT-N细胞，包括但不限于中风，阿尔茨海默氏病，帕金森氏病和与年​​龄相关的记忆障碍。为了实现这一目标，我们需要探索ACT-N细胞在疾病和/或受伤期间在中枢神经系统中激活的天然修复机制的潜在能力，并通过使用必要的安全性，质量和过程控制来开发可靠和可再现的制造策略。关于后者的需求，该研究计划旨在确定与它们得出的MDC不同的ACT-N细胞的独特特征，包括免疫表型，DNA甲基化水平和分化潜力。此外，将解决与ACT N安全有关的初步考虑。