Recellularization of Liver Bioscaffolds

肝脏生物支架的再细胞化

基本信息

批准号：
9754808
负责人：
Basak Elif Uygun
金额：
$ 39.54万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-05 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9754808
关键词：
Address Affinity Architecture Biliary Binding Biomaterials Research Blood Vessels Cells Cessation of life Collagen Cues Data Development Elastin Endothelial Cells Endothelium Engineering Epithelial Cells Extracellular Matrix Extrahepatic Bile Ducts Future Goals Graft Survival Health Hepatic Hepatic Mass Hepatocyte Human Image Analysis In Vitro Kidney Lead Liver Liver Dysfunction Liver Failure Liver Regeneration Liver diseases Location Modeling Organ Organ Donor Organ Model Organ Transplantation Pancreas Peptides Perfusion Protocols documentation Public Health Rattus Research Seeds System Techniques Testing Time Tissue Engineering Transplantation Vascular Endothelial Cell Waiting Lists Work base bile duct biliary tract blood perfusion cell type clinical translation density end-stage organ failure graft function in vivo liver function liver transplantation neglect next generation novel strategies public health relevance scaffold success thrombogenesis

项目摘要

Abstract About thirty million people in the US have some type of liver disorder, and about 27,000 deaths are registered annually due to liver disease. At this time, the only definitive treatment of hepatic failure is orthotopic transplantation. However, there is a critical shortage of organs with a continual deficit of >4,000 livers per year. Given that only organs in pristine condition are transplantable, orthotopic transplantation will always remain a limited pool. Recent advances in tissue engineering through the use of decellularized liver scaffolds have opened the possibility that engineered liver grafts could be used as substitutes for donor livers, potentially addressing the shortage of organs available for transplantation. However, the road to clinical translation is expected to be long due to the wide range of functions the engineered liver is required to capture, for example, those represented by the biliary system have been neglected thus far. Furthermore, long term transplantation of engineered liver grafts has not been successful due to thrombogenicity of the recellularized grafts. We plan to engineer transplantable liver grafts for treating liver dysfunction and failure through the completion of the following specific aims 1) Enhance endothelialization efficiency of rat liver grafts, 2) Repopulate bile ducts of rat livers and 3) Develop a liver graft that functions in vivo. The work described here is expected to result in the next generation engineered liver grafts incorporating parenchymal and non-parenchymal components to provide auxiliary hepatic support.

抽象的美国约有 3000 万人患有某种类型的肝脏疾病，登记的死亡人数约为 27,000 人每年因肝病。目前，肝衰竭唯一确定的治疗方法是原位治疗移植。然而，器官严重短缺，每年持续短缺超过 4,000 个肝脏。鉴于只有处于原始状态的器官才可移植，原位移植始终是一种有限池。通过使用脱细胞肝脏支架在组织工程方面取得的最新进展开启了工程肝移植可用作供体肝脏替代品的可能性解决可用于移植的器官短缺问题。然而，临床转化之路是由于工程肝脏需要捕获广泛的功能，因此预计会很长，例如，迄今为止，以胆道系统为代表的那些一直被忽视。此外，长期移植由于再细胞化移植物的血栓形成性，工程化肝移植物的研究尚未成功。我们计划通过完成以下项目来设计可移植肝移植物以治疗肝功能障碍和衰竭以下具体目标 1) 增强大鼠肝移植物的内皮化效率，2) 重建大鼠胆管肝脏；3) 开发可在体内发挥作用的肝移植物。这里描述的工作预计会导致下一代工程肝移植物结合实质和非实质成分提供辅助肝脏支持。