权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Computer-aided Development of a Liver Organ Culture System

肝器官培养系统的计算机辅助开发

基本信息

批准号：
7806755
负责人：
Korkut Uygun
金额：
$ 0.11万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7806755
关键词：
Advisory Committees Applications Grants Bile fluid Biochemical Pathway Biomedical Engineering Calculi Cardiac Death Cessation of life Chemical Engineering Chronic Cirrhosis 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 Failure Liver diseases Mammalian Cell Massachusetts Medicine Metabolic Methodology Methods Mitochondria Modeling Natural regeneration Operative Surgical Procedures Organ Organ Culture Techniques Organ Donor Organ Preservation Oxygen Patients Perfusion Probability Production Public Health Rattus Reperfusion Injury Research Research Personnel Resuscitation Simulate Solutions Study Section System Systems Biology Technology Testing Time Training Transplantation Urea Waiting Lists Work base body system career career development 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

项目摘要

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. Relevance to public health: Chronic liver disease and cirrhosis causes about 27,000 deaths annually in the US, 2,500 of which perish on the waiting list for liver transplant. A major reason of liver related deaths is the limited donor pool. This project aims to improve public health by utilizing currently discarded donor livers by reconditioning them to be transplantable with success. x

这是Uygan博士的职业资助申请；他是一名训练有素的化学工程师，专门从事复杂系统的数学建模和优化。乌伊贡博士最近开发了一部小说建立肝细胞模型的方法，他的兴趣已经转移到这些工具在生物医学中的应用上工程学。致。在生物医学系统领域确立自己的独立研究员地位工程师，Uygan博士在Martin博士的赞助下提交了这份五年职业发展计划 Yarmush，哈佛医学院外科和生物工程教授海伦·安德鲁斯·本尼迪克特马萨诸塞州总医院医学工程中心主任包括一)生物医学工程和隔离肝脏灌流方面的强化实践培训，二)学术课程和研讨会，以及iii)一个特别咨询委员会的指导。项目概述：这项研究的长期目标是开发肝脏代谢工程治愈或治疗相关疾病的方法，包括脂肪变性和纤维化，并减少死亡一般都是因为肝功能衰竭。这项拟议的研究的目标是在硅胶和体外培养配对灌流肝脏模型，并将其用于边缘肝脏的代谢工程以增加供体游泳池。这里要检验的中心假设是，肝脏在体外可以保持功能通过优化代谢调节来延长周期，这种器官培养系统可以用于复苏缺血肝脏和脱脂供移植。其基本原理是开发一种将代谢活动和生存能力相关联的硅肝模型将使模拟大量高效的代谢调节策略，识别出数量有限的候选补充能量水平的脱脂解决方案，从而实现肝脏灌流的新陈代谢优化在项目期内实际操作。这里描述的工作有望：1)建立常温体外灌流作为一种可行的功能性肝脏存储手段，ii)产生一个在计算机上的模型分离的灌流大鼠肝脏，将代谢功能、肝脏损伤和移植成功联系起来，以及建立新的方法，使边缘肝移植成为可能，从而减少与肝功能衰竭相关的死亡。这项工作的结果也将对肝脏器官规模的研究产生积极影响，例如脂肪变性、纤维化和再生，通过提供一个稳定和完善的系统作为基础。与公共卫生的相关性：慢性肝病和肝硬变每年导致约27,000人死亡美国，其中2500人在等待肝脏移植的名单上死亡。与肝脏相关的死亡的一个主要原因是有限的捐赠者池。该项目旨在通过利用目前被丢弃的捐赠者肝脏来改善公共卫生成功地对它们进行了改造，使其可移植。X