Performance of a flat membrane bioreactor utilizing porcine hepatocytes cultured in an extracellular matrix

Abstract

To be clinically successful, an extracorporeal bioartificial liver (BAL) should allow maintenance of liver specific functions in vitro and achievement of high density cell culture for minimising the size of the BAL. The module must be designed to ensure optimum conditions for the mass transfer of nutrients and oxygen that are required for cell survival and metabolism. On this basis, it is generally agreed that there is room for improvement in bioreactor design. The majority of the current bioreactor designs do not fully meet these requirements. This could result in a situation in which BALs perform well for limited periods of time after which the hepatocytes deteriorate rapidly. In this respect, we consider that the impact of bioreactor design on hepatocyte viability and functions has been grossly undervalued. It is our view that when designing a BAL, special attention should be paid to providing the architectural basis for reconstructing a proper cellular microenvironment that ensures the highest and prolonged functional activity of hepatocytes cultured in the bioreactor. Tissue architecture and parenchymal cell morphology are crucial for the proper functioning of hepatocytes within the organ in situ. In the liver, hepatocytes are organized three-dimensionally into cellular plates that are identified as cords in a cross-sectional view. In these plates hepatocytes exhibit a distinctive epithelial polarity, as well as a strongly developed cell-cell communication structures including bile canaliculi and tight junctions. Thus, hepatocytes must interact with other cells as well as with chemically complex substrata to sustain viability and functions. This organisation allows them to obtain an adequate supply of oxygen and nutrients.