Directing Embryonic Stem Cells to Hepatocytes
将胚胎干细胞引导至肝细胞
基本信息
- 批准号:6857928
- 负责人:
- 金额:$ 14.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-09-30 至 2006-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Treatment of liver disease with orthotopic liver transplantation (OLT) carries considerable morbidity and mortality. Moreover, due to organ shortages, thousands of people die each year without getting transplanted. Therefore, safer and more convenient alternative therapies will benefit many people requiring liver transplantation. An approach that might address this problem is the development of a proliferative cell line that expresses liver-specific genes which could be employed for cell transplantation or for a bioartificial liver. Developing such a line from human embryonic stem cells (ESC) would provide cells valuable for pharmacology and toxicology studies, as well as establishing an approach that could be employed in human cells. Specific Aims: 1) to determine conditions for directing the ESC to differentiate into hepatocytes in vitro, and to characterize the differentiated cells; and 2) to establish the in vivo potential of human ESC. Methods: A variety of conditions will be empirically assayed to delineate the most effective approach to differentiate the embryonic cells along a hepatocyte lineage. The NIH code number of the cells that are being used is WA01. To delineate mechanisms aimed at inducing either proliferation or hepatocellular gene expression in the cells, specific manipulations will be utilized with assays of liver-specific gene products and growth factor responsiveness. To determine whether the cells can engraft, survive and proliferate after transplantation, studies will be conducted in immunodeficient NOD-SCID mouse models. Health Relatedness: If the studies are successfully undertaken, it will provide for the development of an unlimited source of differentiated human hepatocyte-like cells that can be employed in cell-based therapeutics or in pharmacology studies.
描述(由申请人提供): 原位肝移植(奥尔特)治疗肝病具有相当高的发病率和死亡率。此外,由于器官短缺,每年有数千人在没有得到移植的情况下死亡。因此,更安全,更方便的替代疗法将使许多需要肝移植的人受益。一种可能解决这个问题的方法是开发一种表达肝脏特异性基因的增殖细胞系,该细胞系可用于细胞移植或生物人工肝。从人类胚胎干细胞(ESC)中开发这样一个细胞系将为药理学和毒理学研究提供有价值的细胞,并建立一种可用于人类细胞的方法。具体目标:1)确定指导ESC体外分化为肝细胞的条件,并表征分化的细胞;和2)建立人ESC的体内潜力。研究方法:将根据经验测定各种条件以描绘使胚胎细胞沿着肝细胞谱系分化的最有效方法。正在使用的细胞的NIH代码为WA 01。为了描述旨在诱导细胞增殖或肝细胞基因表达的机制,将使用特定的操作与肝脏特异性基因产物和生长因子反应性的测定。为了确定细胞是否可以在移植后植入、存活和增殖,将在免疫缺陷NOD-SCID小鼠模型中进行研究。健康相关性:如果研究成功进行,将为开发可用于基于细胞的治疗或药理学研究的分化的人肝细胞样细胞的无限来源提供条件。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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MARK ALLEN ZERN其他文献
MARK ALLEN ZERN的其他文献
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{{ truncateString('MARK ALLEN ZERN', 18)}}的其他基金
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