NOVEL APPLICATION OF STEM CELLS/ RETROVIRAL VECTORS

我们实验室和其他人最近的研究表明， 造血干细胞和其他来源于 非造血器官，可能具有分化成造血干细胞的能力。 一系列成熟细胞类型与最初认为的不同 来自细胞。干细胞群体的这种明显的“可塑性” 为扩大骨髓的使用提供了新的机会， 移植结合基因转移治疗先天性 影响血液以外细胞的疾病。这种战略 可能对于治疗其中 细胞或基因在整个身体中的系统递送是必要的， 肌肉萎缩症 在本研究计划中，我们建议（i） 以全面的方式确定细胞类型的谱， 来源于分离自不同细胞群的干细胞， （二）制定隔离、操纵和 - 移植细胞，其导致优化的生产， 特定细胞类型的系统性植入，和（iii）应用那些 程序，沿着我们以前开发的方法， 造血干细胞的转导，以评估基因 治疗特定先天性疾病的疗法，使用良好 特征动物模型。

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.