HEMATOPOIETIC STEM CELL DERIVED HEPATOCYTES

描述(由申请人提供)： 这项研究计划的目标是确定允许 造血干细胞(HSC)分化为肝细胞。该项目 本提案中详细介绍的是基于小鼠肝脏再生的模型。 具体地说，我们建议：1)测试单个高度纯化的HSC是否能够 分化为造血系和肝系。2)进行 不同来源高纯度肝星状细胞的比较研究 目的为肝移植确定最佳的HSC来源。3)至 检查造血植入是否是肝细胞的必经步骤 差异化。4)过渡中间单元的特征 肝星状细胞和肝细胞之间的关系。5)测试HSC是否可以为其他 非造血组织。6)检测人类HSC是否具有分化能力 转化为肝细胞。 这些发现结合在一起，可以确定HSC的关键因素 可塑性。我们认为HSC来源的肝细胞可能是 基于细胞的疗法的发展应对了无数毁灭性的 人类的肝病。

DESCRIPTION (provided by applicant): The goal of this research program is to identify the mechanisms that allow hematopoietic stem cells (HSC) to differentiate into hepatocytes. The project detailed in this proposal is based on a mouse model for liver regeneration. Specifically we propose: 1) To test whether a single, highly purified HSC can differentiate into both the hematopoietic and hepatic lineage. 2) To conduct comparative studies between highly purified HSC from different sources with the aim of defining the best source of HSC for hepatic engraftment. 3) To examine whether hematopoietic engraftment is an obligatory step for hepatocyte differentiation. 4) Characterization of a transitional intermediate cell between HSC and hepatocytes. 5) To test whether HSC can contribute to other non-hematopoietic tissues. 6) To test whether human HSC can differentiate into hepatocytes. These discoveries together enable the identification of key factors for HSC plasticity. We propose that HSC-derived hepatocytes could be the basis for the development of cell-based therapeutics addressing a myriad of devastating human liver diseases.