Computer-aided Development of a Liver Organ Culture System

肝器官培养系统的计算机辅助开发

• 批准号: 8244562
• 负责人: Korkut Uygun
• 金额: $ 26.65万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8244562
• 关键词: Advisory Committees; Applications Grants; Bile fluid; Biochemical Pathway; Biomedical Engineering; Calculi; Cardiac Death; Cessation of life; Chemical Engineering; Complex; Computer Assisted; Computer Simulation; Cryopreservation; Data; Deposition; Development; Development Plans; Disease; Employment; Engineering; Environment; Fatty Liver; Fibrosis; General Hospitals; Goals; Gold; Hand; Hepatocyte; Hour; Ischemia; Lipids; Liver; Liver Cirrhosis; Liver Failure; Mammalian Cell; Massachusetts; Medicine; Metabolic; Methodology; Methods; Mitochondria; Modeling; Natural regeneration; Operative Surgical Procedures; Organ; Organ Culture Techniques; Organ Donor; Oxygen; Patients; Perfusion; Principal Investigator; Probability; Production; Public Health; Rattus; Reperfusion Injury; Research; Research Personnel; Simulate; Solutions; System; Systems Biology; Technology; Testing; Time; Training; Transplantation; Urea; Waiting Lists; Work; base; body system; career; career development; chronic liver disease; improved; innovation; interest; liver function; liver metabolism; liver preservation; liver transplantation; mathematical model; medical schools; microorganism; novel; nutrition; prevent; professor; programs; repaired; success; tool; uptake

This is a career grant application for Dr. Uygun; a chemical engineer by training who specializes in mathematical modeling and optimization of complex systems. Dr. Uygun has recently developed novel methods of modeling hepatocytes, and his interests have shifted to application of such tools to biomedical engineering. To. establish himself as an independent researcher in the field of biomedical systems engineering, Dr. Uygun submits this five-year career development plan under the sponsorship of Dr. Martin Yarmush, the Helen Andrus Benedict Professor of Surgery and Bioengineering at Harvard Medical School and the director of the Center for Engineering in Medicine at the Massachusetts General Hospital, which includes i) intensive hand-on training in biomedical engineering and isolated liver perfusion, ii)academic courses and seminars, and iii) guidance of a select advisory committee. Project Summary: The long-term goals of this research are to develop liver metabolic engineering methodologies for curing or treating relevant diseases including steatosis and fibrosis, and reducing deaths due to liver failure in general. The objectives of the proposed study are to develop paired in silico and ex vivo perfused liver models, and utilize them for metabolic engineering of marginal livers to increase the donor pool. The central hypothesis to be tested here is that the liver can be maintained functionally ex vivo for extended periods by optimal metabolic modulation, and this organ culture system can be employed for resuscitating ischemic livers and defatting steatotic livers for transplantation. The rationale is that the development of an in silico liver model that correlates metabolic activity and viability will enable simulating a large number of metabolic modulation strategies efficiently, identifying a limited number of candidate solutions for defatting of repleting energy levels, hence rendering metabolic optimization of perfused livers practical within the project period. The work described here is expected to i) establish normothermic extracorporeal perfusion as a feasible means of functional liver storage, ii) generate an in silico model of the isolated perfused rat liver that correlates metabolic functioning, liver damage and transplant success, and iii) establish novel methods to enable transplantation of marginal livers, thereby reducing liver failure related deaths. The results of this work will also have a positive impact on organ scale research of the liver, such as steatosis, fibrosis and regeneration, by providing a stable and well-characterized system as their basis.

这是一份维根博士的职业资助申请；化学工程师受过训练的化学工程师，专门从事