Human induced pluripotent stem cell (iPSC) technology combined with a hollow fiber based bioartificial liver (BAL) device can benefit patients with liver failure. Defined iPSC lines can provide unlimited supply of functional hepatocytes by developing iPSC derived hepatocytes (iHeps). Disclosed herein is a protocol for deriving metabolically active hepatocytes from iPSCs. In some embodiments, iHeps were cultured on microcarrier beads in spinner flasks. Subsequently, the iHep-microcarrier complexes were loaded into the extracapillary space of a hollow fiber bioreactor cartridge and cultured using closed circuit continuous flow system. The iHeps secreted human albumin, prothrombin and apolipoprotein B into the hollow fiber intracapillary space media which indicated the maintenance of plasma protein secretory function. In addition, the continuous flow system improved the maturation of iHeps. Thus, the iPSC hepatocytes in the bioartificial liver device maintained the secretory function and exhibited cell maturation.
