Engineering a Functional Liver Graft for Treatment of End Stage Liver Disease

设计功能性肝移植来治疗终末期肝病

基本信息

批准号：
8463800
负责人：
Denver Michael Faulk
金额：
$ 1.61万
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：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8463800
关键词：
3-Dimensional Address Autologous Bile fluid Biomedical Engineering Blood Circulation Blood Vessels Bolus Infusion Cell Adhesion Cell Count Cell Survival Cell Transplantation Cell-Matrix Junction Cells Cessation of life Chronic Cicatrix Clinical Comb animal structure Complex Cues Development Drainage procedure Engineering Engraftment Extracellular Matrix Foundations Future Goals Health Hepatic Hepatic Cord Hepatic Tissue Hepatocyte Honey Immune response Immunosuppressive Agents Implant In Situ Inflammatory Investigation Label Liver Liver Failure Liver Regeneration Liver diseases Location Methods Modeling Morbidity - disease rate Nutrient Organ Organ Donor Organ Transplantation Patients Perfusion Phenotype Physiological Portal vein structure Public Health Rattus Regenerative Medicine Regimen Research Risk Shapes Signal Transduction Spatial Distribution Staging Structure System Techniques Testing Therapeutic Tissues Translations Transplantation United States Work aging population base cell type drug discovery hepatic vein implantation in vivo liver transplantation macrophage older patient reconstitution research study scaffold success

项目摘要

DESCRIPTION (provided by applicant): Approximately 27,000 deaths occur annually in the United States alone from patients with end-stage liver disease. With an aging population, this number is only expected to increase. The current definitive treatment is orthotropic transplantation. However, due to high demand there exists a critical shortage of donor livers. Those patients fortunate enough to receive a transplant are burdened with the risk of chronic rejection and the morbidity associated with a lifelong regimen of immunosuppressant therapy. This treatment is especially difficult for elderly patients. This application addresses a regenerative medicine strategy for engineering an implantable liver graft for patients with end-stage liver failure. It is based upon three fundamental concepts: 1) the native ECM of the liver, including the three dimensional untrastructure and composition, represents an ideal and required substrate for liver regeneration, 2) whole liver ECM scaffolds retain the three-dimensional macrostructure, the native microvascular network, and the bile drainage system; allowing for complete recellularization of all native cell types, and 3) liver regeneration can be promoted when reseeded whole liver ECM grafts are placed in the appropriate three dimensional microenvironment; specifically, in-situ in patients with liver failure. The objectives f the proposed research are to (1) establish an effective method for reseeding a three- dimensional liver scaffold, with a focus on systematically seeding both parenchymal and non parenchymal cells in their native location and to (2) evaluate the host response to the implantation of a reseeded three- dimensional liver scaffold. Additionally, the methods and techniques developed in this study present an important step towards the establishment of decellularization and recellularization criteria necessary to successful produce the first fully functional bioengineered livers for organ transplantation and drug discovery.

描述（由申请人提供）：仅在美国，大约27,000人死亡。随着人口老龄化，这一数字仅有望增加。当前的最终治疗是正交性移植。但是，由于需求量很高，供体肝脏的严重短缺。这些患者幸运地接受移植的患者承受着慢性排斥的风险以及与免疫抑制剂治疗的终身治疗方案相关的发病率。对于老年患者而言，这种治疗尤其困难。该申请涉及针对末期肝衰竭患者的植入肝移植的再生医学策略。它基于三个基本概念：1）肝脏的本地ECM，包括三维联合结构和组成，代表了肝脏再生的理想且必需的底物，2）全肝ECM支架保留了三维宏观结构，即三维宏观结构，本机微血管网络和少量排水系统；允许所有天然细胞类型的完全覆盖，3）当回收的整个肝ECM移植物都放在适当的三维微环境中时，可以促进肝脏再生；具体而言，肝衰竭患者的原位。拟议的研究的目标是（1）建立一种有效的方法来恢复三维肝支架，重点是系统地在其本地位置系统地播种实质和非实质细胞，并评估（2）评估宿主对已恢复的三维liver liver caffold植入的宿主反应。此外，这项研究中开发的方法和技术提出了建立脱细胞化和延细标准的重要一步，以成功生产出第一个功能齐全的生物工程肝脏，以进行器官移植和药物发现。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The effect of detergents on the basement membrane complex of a biologic scaffold material.

DOI：
10.1016/j.actbio.2013.09.006
发表时间：
2014-01
期刊：
ACTA BIOMATERIALIA
影响因子：
9.7
作者：
Faulk, D. M.;Carruthers, C. A.;Warner, H. J.;Kramer, C. R.;Reing, J. E.;Zhang, L.;D'Amore, A.;Badylak, S. F.
通讯作者：
Badylak, S. F.