Engineering of hepatic grafts with decellularized native matrices

使用脱细胞天然基质进行肝移植工程

基本信息

批准号：
8508932
负责人：
Alejandro Soto-Gutierrez
金额：
$ 22.48万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-20 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8508932
关键词：
Advisory Committees Animal Model Apoptotic Applications Grants Biomedical Engineering Cell Therapy Cells Cessation of life Commit Cues Cytoskeleton Development Development Plans Doctor of Medicine Doctor of Philosophy Employment Engineering Engraftment Environment Future General Hospitals Goals Hand Hepatic Hepatocyte Implant In Vitro Instruction Lead Liver Liver diseases Lobe Massachusetts Medicine Methods Operative Surgical Procedures Organ Organ Culture Techniques Patients Perfusion Protocols documentation Public Health Rattus Research Personnel Stem cells System Techniques Testing Training Transplantation Waiting Lists Work base career career development cell motility cell type improved interest liver transplantation medical schools metabolic engineering novel professor scaffold stem stem cell differentiation success tool

Advisory Committees Animal Model Apoptotic Applications Grants Biomedical Engineering Cell Therapy Cells Cessation of life Commit Cues Cytoskeleton Development Development Plans Doctor of Medicine Doctor of Philosophy Employment Engineering Engraftment Environment Future General Hospitals Goals Hand Hepatic Hepatocyte Implant In Vitro Instruction Lead Liver Liver diseases Lobe Massachusetts Medicine Methods Operative Surgical Procedures Organ Organ Culture Techniques Patients Perfusion Protocols documentation Public Health Rattus Research Personnel Stem cells System Techniques Testing Training Transplantation Waiting Lists Work base career career development cell motility cell type improved interest liver transplantation medical schools metabolic engineering novel professor scaffold stem stem cell differentiation success tool

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项目摘要

This is a career grant application for Dr. Soto-Gutierrez; an M.D.; Ph.D. who specializes in cell therapies and liver diseases. Dr. Soto-Gutierrez has recently developed novel methods of differentiating stem cells into liver cells, and his interests have shifted to application of such tools to organ engineering. To establish himself as an independent researcher in the field of organ engineering, Dr. Soto-Gutierrez submits this fiveyear 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 organ engineering, isolated liver-matrices perfusion and stem cell differentiation, ii)academic courses and seminars, and iii) guidance of a select advisory committee. Our long-term goals are to develop a natural hepatic platform for complete and stable maturation of stemderived liver cells and to engineer functional liver grafts. The objectives of the proposed study are to develop an extracorporeal perfusion liver-matrix-scaffold system for repopulation and hepatic maturation of stem liver-derived cells, and investigate its employment for the creation of auxiliary liver grafts for transplantation in patients with impaired hepatic function. The central hypothesis to be tested here is that the decellularized natural liver scaffold, obtained from discarded livers, can be extensively repopulated and can provide an adequate maturation environment for stem derived liver cells, and this organ culture system can be employed to engineer metabolic functional liver grafts for transplantation. The rationale of the study is that ischemically damaged, untransplantable organs are available in numbers that far surpass the current demand, and they present an ideal platform for delivery for stem cell-based therapies. The work described here is expected to i) establish a protocol for recellularization and engraftment of hepatocyes in decellularized matrices, ii) generate a repopulation and maturation system for stem cell-derived hepatocytes, and iii) develop a novel method of liver graft engineering for transplantation as auxiliary liver support in hepatic diseases. The results of this work will also have a positive impact by establishing the basis and platform for future sophisticated organ engineering techniques that incorporates several different cell types, can be applied to other organs and may lead to development of entire organs in vitro.

这是Soto-Gutierrez博士的职业赠款申请； An M.D。;博士谁专门从事细胞疗法和肝病。 Soto-Gutierrez博士最近开发了将干细胞区分化为肝细胞及其兴趣已转移到了这样的工具上的应用中。建立 Soto-Gutierrez博士本人是器官工程领域的独立研究员，提交了这五年在马丁·雅尔穆什（Martin Yarmush）博士的赞助下，海伦·安德鲁斯·本尼迪克特（Helen Andrus Benedict）哈佛医学院外科和生物工程教授和中心主任马萨诸塞州综合医院的医学工程，其中包括i）强化手工培训在器官工程中，孤立的肝脏灌注和干细胞分化，ii）学术课程和研讨会和iii）精选咨询委员会的指导。我们的长期目标是建立一个自然的肝平台，以使STEMDEDERDER的完整和稳定成熟肝细胞和设计功能性肝移植物。拟议的研究的目标是发展体外灌注肝马托里克斯 - 体系，用于重生和肝成熟的肝脏成熟肝脏衍生的细胞，并调查其用于创建辅助肝移植的就业在肝功能受损的患者中。这里要测试的中心假设是脱细胞自然肝脚手架，从废弃的肝脏获得，可以广泛重新填充，可以提供茎衍生的肝细胞的足够成熟环境，该器官培养系统可以是用于设计代谢功能性肝移植物进行移植。该研究的理由是在缺口上损坏，不可转移的器官的数量远远超过电流需求，它们是基于干细胞疗法的理想平台。描述的工作 i）在这里预计i）建立了hepatocyes延迟和植入的方案脱细胞矩阵，ii）生成一个用于干细胞衍生的肝细胞的重生和成熟系统， iii）开发了一种新颖的肝移植工程方法，用于移植作为辅助肝支持肝病。这项工作的结果还将通过建立基础和未来复杂的器官工程技术的平台，结合了几种不同的细胞类型，可以应用于其他器官，并可能导致整个器官在体外的发展。