Recellularization of Liver Bioscaffolds

摘要 在美国，约有3000万人患有某种类型的肝病，约有2.7万人死亡 每年因肝病。此时，肝功能衰竭的唯一权威治疗方法是原位治疗。 移植。然而，器官严重短缺，每年持续缺乏4000个肝脏。 鉴于只有处于原始状态的器官才能移植，原位移植将永远是一种 有限的游泳池。利用脱细胞肝支架进行组织工程的最新进展 开启了工程肝移植被用作供体肝脏替代品的可能性，潜在地 解决可供移植的器官短缺问题。然而，通往临床翻译的道路是 由于工程肝脏需要捕获的功能范围很广，例如， 到目前为止，以胆道系统为代表的那些被忽视了。此外，长期移植 由于再细胞化移植物的血栓形成能力，工程化肝移植物的临床应用并不成功。我们计划 设计可移植肝移植以治疗肝功能障碍和衰竭 遵循特定的目标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)开发一种能在体内发挥作用的肝移植。这里描述的工作预计将导致 融合实质和非实质成分的下一代工程化肝移植 提供辅助性肝脏支持。

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.