Engineering Embryonic Stem Cell Differentiation into Hepatocytes

工程胚胎干细胞分化为肝细胞

• 批准号: 7320278
• 负责人: Arno W Tilles
• 金额: $ 11.81万
• 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/7320278
• 关键词: Activities of Daily Living; Adult; Advisory Committees; Albumins; Animal Sources; Animals; Artificial Liver; Award; Basic Science; Biochemical; Biomedical Engineering; Bioreactors; Breeding; Cell Communication; Cell Differentiation process; Cell model; Cells; Cellular biology; Clinical Research; Coculture Techniques; Collagen; Communities; Complex; Condition; Core Facility; Cultured Cells; Detection; Development; Devices; Drug Metabolic Detoxication; Embryo; Embryonic Development; Engineering; Ensure; Environment; Enzymes; Excision; Extracellular Matrix; Faculty; Fellowship; Fluorescence-Activated Cell Sorting; Fostering; General Hospitals; Generations; Goals; Gold; Green Fluorescent Proteins; Hepatic Tissue; Hepatocyte; Hospitals; Human; In Vitro; Internal Medicine; Knowledge; Liver; Massachusetts; Medical Students; Medicine; Mentors; Mentorship; Metabolic; Microfluidics; Microscopic; Movement; Mus; Numbers; Operative Surgical Procedures; Organ; Patients; Physicians; Population; Postdoctoral Fellow; Principal Investigator; Program Development; Purpose; Range; Research; Research Personnel; Residencies; Scientist; Signal Transduction; Source; Standards of Weights and Measures; Stem cells; Students; Surface; System; Techniques; Technology; Testing; Time; Tissue Engineering; Training; Training Programs; Universities; Variant; authority; career; cell motility; design; embryonic stem cell; genetically modified cells; high throughput screening; matrigel; medical schools; mouse model; precursor cell; professor; programs; promoter; protein expression; response; stem; synthetic protein

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项为期五年的培训计划，旨在发展作为医师科学家和生物医学工程师的学术职业。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)/哈佛医学院完成了研究奖学金。他的职业目标是建立一个专注于肝组织工程和生物人工肝 (BAL) 开发的前沿研究项目。 通过教学课程和指导计划，PI 将重点研究胚胎干细胞生物学。 Martin Yamush 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 Pl 的导师。他是麻省总医院外科教授兼医学工程中心主任。他指导了许多生物医学工程博士后和研究生。麻省总医院医学系副教授、干细胞生物学权威 David Scadden 博士将担任该项目的联合导师。他指导了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。 该提案的研究重点是开发在体外从胚胎干（ES）细胞衍生成体肝细胞的技术。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）开发微流控生物反应器，用于胚胎干细胞分化为肝细胞的高通量表征； (2)利用固定化和可溶性因子调控胚胎干细胞向成熟肝细胞的分化； (3)利用代谢工程原理表征分化的细胞群并优化其器官特异性功能的表达。这些研究将提供基础知识和技术，使 PI 能够为 BAL 装置开发稳定的肝细胞来源。 MGH 外科医学工程中心和哈佛医学院社区为 PI 的职业生涯提供了良好的环境。杰出的师资队伍、跨学科的环境、装备精良的核心设施以及广泛的协作互动将为PI提供追求和实现其职业目标所需的一切。