Pilot Feasibility Project #3

试点可行性项目

• 批准号: 7900541
• 负责人: SCOTT L. FRIEDMAN
• 金额: $ 3.81万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7900541
• 关键词: Address; Adult; Alcoholic Liver Diseases; Alcohols; Biological Models; Cell Line; Cells; Chronic; Coculture Techniques; Development; Embryo; Endoderm; Endothelial Cells; Fibrosis; Goals; Hepatic; Hepatocyte; Human; In Vitro; Injury; Intestines; Kupffer Cells; Liver; Liver Failure; Lung; Modeling; Mus; Organ; Pancreas; Regulation; Source; Staging; Study models; System; Thyroid Gland; Translating; Transplantation; United States National Institutes of Health; embryonic stem cell; human embryonic stem cell; in vitro Model; oxidant stress; progenitor; programs; research study; stellate cell; stem; stem cell differentiation

The capacity of embryonic stem (ES) cells to differentiate to hepatocytes in culture provides a unique model system to study alcohol-induced liver injury in vitro, and ultimately to provide large amount of mature hepatocytes for transplantation in liver failure due to chronic alcoholic liver disease. Liver develops from the gut endoderm along with other major organs including the pancreas, lungs, thyroid and intestines. The experiments outlined in the proposal build on previous observations that endoderm-derived hepatoblast-like cells can be efficiently and reproducibly induced in the mouse ES cell system and seek to translate the murine ES cell differentiation program to the human ES cell program"!. This application addresses questions relating to maturation of mouse ES-derived hepatoblast-like cells, to the endoderm induction in the human ES cell system and its specification to a hepatic fate and finally to mature human hepatocytes. Therefore, the ultimate goal of these studies is to develop a feasible approach to generate functional hepatocytes from mouse and human ES cells as an in vitro model to study alcohol-induced liver injury.

胚胎（ES）细胞在培养中区分肝细胞的能力提供了独特的模型 研究酒精诱导的体外肝损伤的系统，并最终提供大量成熟 由于慢性酒精性肝病而导致的肝衰竭移植肝细胞。肝脏从 肠道内胚层以及其他主要器官，包括胰腺，肺，甲状腺和肠。这 提案中概述的实验基于先前的观察结果，这些观察结果是内胚层衍生的肝细胞状的 细胞可以在小鼠ES细胞系统中有效且可重复诱导，并试图翻译 对人ES细胞计划的鼠类ES细胞分化程序”！该应用程序解决了问题 与小鼠ES衍生的肝细胞样细胞的成熟有关，与人类的内胚层诱导有关 ES细胞系统及其对肝脏命运的规范，最后是成熟的人肝细胞。因此， 这些研究的最终目标是开发一种可行的方法，以产生功能性肝细胞 小鼠和人类ES细胞是研究酒精诱导的肝损伤的体外模型。