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.
Treatment for end-stage organ failure is restricted by the critical shortage of donor organs with the organ waiting list currently at 100,000 requests and it is increasing by 5% every year. In the case of liver, about 4,000 people die in US while waiting for a transplantable organ, and the lack of donor organs is considered a major health crisis. This project aims to advance public health by developing transplantable liver grafts.
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