Recellularization of Liver Bioscaffolds

肝脏生物支架的再细胞化

• 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
• 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

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病，大约27,000人死亡已注册 每年由于肝病。目前，肝衰竭的唯一明确治疗方法是原位 移植。但是，每年持续赤字的器官持续不断降低，肝脏持续不断。 鉴于只有原始条件下的器官是可以移植的，因此原位移植将始终保持 有限的池。通过使用脱细胞肝支架，组织工程的最新进展具有 打开了工程肝移植物可以用作供体肝的替代品的可能性，可能 解决可用于移植的器官短缺。但是，通往临床翻译的道路是 由于功能的广泛功能，预计需要工程肝才能捕获，例如 迄今为止，由胆道系统代表的人已被忽略。此外，长期移植 工程肝移植物的结束性移植物的血栓形成尚未成功。我们计划 通过工程移植的肝移植物来治疗肝功能障碍和通过完成 以下特定目的1）提高大鼠肝移植的内皮化效率，2）重新填充大鼠的胆管 肝脏和3）发展一种在体内发挥作用的肝移植物。预计此处描述的工作将导致 下一代工程的肝移植物结合了实质和非副质成分 提供辅助肝支撑。