Development of a Hybrid Liver Support System: A Review

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Abstract
Hybrid liver support systems (LSS) for the use of the detoxifying, metabolic synthetic and regulatory capabilities of liver cells are under development for extracorporeal therapy of acute liver failure and for bridging to liver transplantation. A summary of our development is discussed. A five-step technique for primary liver cell isolation has been introduced in order to address larger scale procurement of hepatocytes. Immobilisation of the cells after isolation appears to be one of the main factors in maintaining hepatocyte function in vitro. Different techniques have been investigated. Using the cell-cell adhesion technique, a culture model was developed for the immobilisation of hepatocytes between capillary membranes. Four separate capillary membrane systems, each forming independent compartments are woven in order to create a three dimensional network. A bioreactor design has been developed. The construction provides different functions, including decentralised cell perfusion. The bioreactor enables 3 dimensional reorganisation of cells, integral oxygenation and decentralised metabolite exchange. The bioreactor has been scaled-up to allow hepatocytes and sinusoidal endothelial cells to be cultured in quantities sufficient for therapeutic application. In a healthy pig model, possible limiting side effects of therapy with this device were excluded. The efficacy of the system has been demonstrated in a hepatectomised pig model. Subsequently, a complete hybrid liver support system for human studies was introduced and applied clinically.