Engineer/Embryonic Stem Cell Differentiation/Hepatocytes

工程师/胚胎干细胞分化/肝细胞

• 批准号: 6846547
• 负责人: Arno W Tilles
• 金额: $ 11.14万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6846547
• 关键词: bioreactors; biotechnology; cell differentiation; cell growth regulation; cell population study; embryonic stem cell; fluid flow; genetic manipulation; high throughput technology; laboratory mouse; liver cells; metabolomics; tissue /cell culture

DESCRIPTION (provided by applicant): This Research Career Award proposal describes a five year training program for the development of an academic career as a physician-scientist and biomedical engineer. The principal investigator (PI), with training as a physician and engineer, completed residency in Internal Medicine at University of Miami/Jackson Memorial Hospital and a research fellowship at Massachusetts General Hospital (MGH)/Harvard Medical School. His career goal is to establish a cutting edge research program focusing on hepatic tissue engineering and bioartificial liver (BAL) development. Through a program of didactic coursework and mentorship, the PI will focus his research efforts on embryonic stem cell biology. Dr. Martin Yarmush, a recognized expert in tissue engineering and metabolic engineering, will serve as the Pl's mentor throughout the course of this project. He is Professor in the Department of Surgery at MGH and the director of the Center for Engineering in Medicine. He has supervised numerous postdoctoral fellows and graduate students in biomedical engineering. Dr. David Scadden, Associate Professor in the Department of Medicine at MGH, and an authority on stem cell biology, will serve as a co-mentor on this project. He has supervised numerous postdoctoral fellows and medical students. A research advisory committee, composed of distinguished physicians, scientists, and engineers, will provide scientific and career guidance to the PI. The research focus in this proposal is to develop techniques to derive adult hepatocytes from embryonic stem (ES) cells in vitro. For the purpose of developing the technology and gaining a better understanding of the underlying basic science, a mouse model will be used. The specific aims are: (1) To develop a microfluidic bioreactor for high throughput characterization of embryonic stem cell differentiation into hepatocytes; (2) To regulate embryonic stem cell differentiation into mature hepatocytes using immobilized and soluble factors; (3) To characterize the differentiated cell populations and optimize their expression of organ specific functions using principles of metabolic engineering. These studies will provide the basic knowledge and technologies enabling the PI to develop a steady source of hepatocytes for BAL devices. The Center for Engineering in Medicine in the Department of Surgery at MGH, and the Harvard Medical School community provide an excellent environment in which to foster the career of the PI. The distinguished faculty, interdisciplinary environment, well equipped core facilities, and extensive collaborative interactions will provide the PI with everything necessary to pursue and launch his career goals.

描述（由申请人提供）： 该研究职业奖提案描述了一个为期五年的培训计划，用于发展作为医生科学家和生物医学工程师的学术生涯。主要研究者（PI）接受过医生和工程师培训，在迈阿密大学/杰克逊纪念医院完成了内科住院医师培训，并在马萨诸塞州总医院（MGH）/哈佛医学院获得了研究奖学金。他的职业目标是建立一个前沿的研究计划，专注于肝组织工程和生物人工肝（BAL）的发展。 通过教学课程和指导计划，PI将专注于胚胎干细胞生物学的研究工作。Martin Yarmush博士是组织工程和代谢工程领域公认的专家，他将在整个项目过程中担任PI的导师。他是麻省总医院外科系教授和医学工程中心主任。他指导过许多生物医学工程的博士后研究员和研究生。大卫斯卡登博士，副教授在医学系在麻省总医院，和权威的干细胞生物学，将作为共同导师对这个项目。他指导过许多博士后研究员和医学生。由杰出的医生、科学家和工程师组成的研究咨询委员会将为PI提供科学和职业指导。 本课题的研究重点是发展胚胎干细胞体外诱导分化成肝细胞的技术。为了开发该技术并更好地了解基础科学，将使用小鼠模型。具体目标是：（1）建立高通量的胚胎干细胞向肝细胞分化的微流控生物反应器;（2）利用固定化因子和可溶性因子调控胚胎干细胞向成熟肝细胞分化;（3）利用代谢工程原理对分化的细胞群体进行表征并优化其器官特异性功能的表达。这些研究将提供基本知识和技术，使PI能够为BAL器械开发稳定的肝细胞来源。 麻省总医院外科医学工程中心和哈佛医学院社区为培养PI的职业生涯提供了良好的环境。杰出的教师，跨学科的环境，设备齐全的核心设施，以及广泛的协作互动将为PI提供追求和启动其职业目标所需的一切。