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开启了新的 治疗各种疾病的概念前沿。一个主要的障碍是 利用这一潜力在于无法控制 移植后的细胞。在这里，我们建议将 人类造血细胞的发育潜力，并开发一种方法 这将允许药物控制的原位扩张 已经从造血性组织过渡到非造血性组织的细胞，使用 以肝脏为模型。我们的方法包括表达一种蛋白质，这种蛋白质可以诱导 细胞在化学二聚体存在的情况下生长。在具体目标上： 我们将测试人类造血细胞的发育潜力。我们会 男性骨髓细胞女性受者尸检组织的研究 以确定男性细胞是否对各种非造血组织有贡献。 在特定目标2中，我们将测试转基因造血细胞 保持肝细胞潜能。雄性小鼠的骨髓将被移植 女性接受者，然后将分析产生的肝细胞 男性捐赠者。在特定目标3中，我们将构建和测试 扩增骨髓来源的肝细胞。在具体目标4中，我们将使用化学物质 体内扩增骨髓来源的肝细胞的二聚剂。

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.