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）：神经退行性疾病和中枢神经系统 (CMS) 损伤 - 例如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症 (ALS) 和中风 - 每年导致数百万美国人残疾和死亡，但这些疾病都没有治愈方法，甚至没有有效的治疗方法。成人大脑中多能神经干细胞（NSC）的发现给神经发生理论带来了革命性的变化；然而，直接从大脑分离的胚胎干细胞和神经干细胞开发的疗法充满了许多技术（肿瘤/畸胎瘤发生、不受控制的多能性、来源、需要免疫抑制）和伦理障碍，阻碍了人类治疗的快速进展。该提案基于一项创新发现，即在特定化学试剂存在下培养的骨髓源性细胞 (MDC) 会产生 ACT-N(tm) 细胞，这些细胞能够迁移并分化为新的神经细胞和神经胶质细胞当植入啮齿动物大脑的侧脑室时。我们的长期目标是开发 ACT-N 细胞作为治疗中枢神经系统衰弱疾病患者的有效疗法，这些疾病包括但不限于中风、阿尔茨海默病、帕金森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 细胞替代和/或增强中枢神经系统在疾病和/或损伤期间激活的天然修复机制的潜在能力，并开发稳健且可重复的制造策略，并提供必要的技术支持。安全、质量和过程控制。针对后者的需求，本研究计划旨在鉴定ACT-N细胞不同于其来源的MDC的独特特征，包括免疫表型、DNA甲基化水平和分化潜力。此外，还将讨论与 ACT-N 安全性相关的初步考虑因素。