![]() However, due to the shortage of available organs, 10% of patients die whilst on the waiting list for an organ, and many more are never considered for transplantation because of the need to optimise graft usage. Despite the enormous scope for prevention of progression to chronic liver disease through vaccination, antiviral therapy, and lifestyle interventions, the only treatment for end-stage liver disease remains liver transplantation. In the United states, 44000 people die of chronic liver disease each year, with an estimated annual hospitalisation costs demonstrating an increasing trend and measured at 18 billion dollars per year in 2016, to which must be added similar magnitude financial costs of pre-hospital healthcare and social care burden.Īlthough vaccination programs and antiviral therapy may result in decreasing prevalence in chronic liver disease of viral aetiology, the consequences of alcohol and hepatic steatosis has resulted in a gradually increasing incidence of chronic liver disease. In the United Kingdom, liver disease is the third commonest cause of premature death, and is associated with societal and health care costs measured in the billions of pounds per annum. Bioengineering by repopulation of decellularised scaffolds has significantly progressed, but there remain significant experimental challenges to be addressed before therapeutic applications may be envisaged.Ĭhronic liver disease is a major health concern, with 1.5 billion individuals affected worldwide, and associated with an annual global mortality of 2 million people. Minority cell groups such as Kupffer cells and stellate cells have not been repopulated. Hepatic vasculature repopulation has enabled sustainable blood perfusion in vivo, but with cell types that would limit clinical applications, and which have not been shown to have the specific functions of liver sinusoidal endothelial cells. Biliary repopulation and function have been restricted by challenges relating to the culture and propagations of cholangiocytes, though advances in organoid culture may help address this. Within these models, a limited but measurable degree of physiologically significant hepatocyte function has been reported with demonstrable ammonia metabolism in vivo. Liver scaffold recellularisation has progressed from small rodent in vitro studies to large animal in vivo perfusion models, using a wide range of cell types including primary cells, cell lines, foetal stem cells, and induced pluripotent stem cells. Decellularisation methodologies vary widely but seek to address the conflicting objectives of removing the cellular component of tissues whilst keeping the 3D structure of the extra-cellular matrix intact, as well as retaining the instructive cell fate determining biochemicals contained therein. Repopulation of decellularised whole organ scaffolds with appropriate cells of recipient origin offers a theoretically attractive solution, allowing reliable and timely organ sourcing without the need for immunosuppression. Liver transplantation is the only curative therapy for end stage liver disease, but is limited by the organ shortage, and is associated with the adverse consequences of immunosuppression.
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