NOVEL APPLICATION OF STEM CELLS/ RETROVIRAL VECTORS

干细胞/逆转录病毒载体的新应用

• 批准号: 6660966
• 负责人: RICHARD C MULLIGAN
• 金额: $ 28.42万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6660966
• 关键词: biotechnology; cell population study; cell type; congenital disorders; disease /disorder model; flow cytometry; gene therapy; hamsters; hematopoietic stem cells; laboratory mouse; stem cell transplantation; stem cells; transfection

Recent studies from our laboratory and others suggest that murine hematopoietic stem cells and perhaps other cell populations derived from non-hematopoietic organs, may possess the capacity to differentiate into a range of mature cell types distinct from those originally thought to be derived from the cells. This apparent 'plasticity' of stem cell populations offers new opportunities to expand the use of bone marrow transplantation, in conjunction with gene transfer, to treat congenital diseases which affect cells other than those of the blood. Such a strategy may be particularly important for the treatment of diseases in which the systemic delivery of cells or genes throughout the body is essential, such as muscular dystrophy. In this research program, we propose to (i) determine, in a comprehensive way, the spectrum of cell types than can be derived from different populations of stem cells isolated from the adult, (ii) to develop procedures for the isolation, manipulation, and transplantation of cells which lead to the optimized production and systemic engraftment of specific cell types, and (iii) to apply those procedures, along with the methods we have previously developed for the transduction of hematopoietic stem cells, to the evaluation of gene therapies for the treatment of specific congenital disease, using well characterized animal models.

我们实验室和其他实验室最近的研究表明，小鼠 造血干细胞，也许还有其他来源于 非造血器官，可能具有分化为 一系列不同于最初认为的成熟细胞类型 从细胞中衍生出来的。干细胞群体的这种明显的“可塑性” 为扩大骨髓的用途提供了新的机会 移植联合基因转移治疗先天性心脏病 影响血液以外的细胞的疾病。这样的战略 可能对疾病的治疗特别重要 全身细胞或基因的系统性传递是必不可少的，例如 作为肌肉营养不良症。在这个研究项目中，我们建议(I) 以一种全面的方式确定细胞类型的光谱 是从不同群体的干细胞中分离出来的 成人，(Ii)制定隔离、操纵和 细胞移植，导致优化生产和 特定细胞类型的系统性植入，以及(Iii)应用这些 过程，以及我们以前为 造血干细胞转导在基因评价中的应用 特殊先天性疾病的治疗方法，用好 典型的动物模型。