Hemopoietic Stem Cell Plasticity

描述（由申请人提供）： 发现干细胞可塑性的意想不到的广度打开了一个新的 治疗各种疾病的概念前沿。 一个主要的障碍， 利用这种潜力在于无法控制发生在一个人身上的事情。 细胞移植后。 在这里，我们建议将 人造血细胞的发育潜力，并开发一种方法， 这将允许在现场控制的膨胀， 已经从造血组织过渡到非造血组织的细胞，使用 肝脏作为模型。 我们的方法包括表达一种蛋白质， 在化学二聚剂存在下的细胞生长。 具体目标I 我们将测试人类造血细胞的发育潜力。 我们将 研究从接受男性骨髓细胞的女性身上提取的尸检组织 以确定雄性细胞是否对各种非造血组织有贡献。 在具体目标2中，我们将测试基因修饰的造血细胞是否 保留肝细胞潜能。 雄性小鼠的骨髓将被移植到 然后分析女性受者的肝细胞， 男性捐赠者 在具体目标3中，我们将构建和测试向量， 扩增骨髓来源的肝细胞。 在具体目标4中，我们将使用化学品 二聚化剂以在体内扩增骨髓来源的肝细胞。

DESCRIPTION (provided by applicant): Discovering the unexpected breadth of stem cell plasticity opens a new conceptual front to treating a wide range of diseases. A major block to exploiting this potential rests in the inability to control what happens to a cell after it has been transplanted. Here we propose to characterize the developmental potential of human hemopoietic cells, and to develop a method that will allow for the pharmacologically controlled in situ expansion of cells that have transited from hemopoietic to non-hemopoietic tissues, using liver as a model. Our approach involves expressing a protein that induces cell growth in the presence of a chemical dimerizing agent. In Specific Aim I we will test the developmental potential of human hemopoietic cells. We will study autopsy tissues taken from female recipients of male bone marrow cells to determine whether male cells contribute to various non-hemopoietic tissues. In Specific Aim 2 we will test whether genetically modified hemopoietic cells retain hepatocyte potential. Bone marrow from male mice will be transplanted into female recipients who will then be analyzed for hepatocytes arising from the male donor. In Specific Aim 3 we will construct and test vectors for expanding marrow derived hepatocytes. In Specific Aim 4 we will use chemical dimerizing agents to expand marrow-derived hepatocytes, in vivo.