On-Chip Differentiation of Radially Vascularized Hepatic Cords Mimicking the Liver Lobule

Due to a more physiological reproduction of the in vivo situation, liver-on-a-chip devices in recent studies have shown higher sensitivity and accuracy for hepatotoxicity testing compared to traditional in-vitro liver models [1][2]. In this context, this work presents an original microfluidic device that mimics 3D microstructured and microfluidically vascularized hepatic cords organized radially like the liver lobule. 10 cell-culture chambers seeded in high density are disposed with parallelized flow that emulates blood perfusion and drug clearance. Using this device, on-chip differentiation of Human HepaRG-hepatoblast (HepaRG-HB) to HepaRG-Hepatocytes (HepaRG-HC) has been studied in terms of self-organization capabilities, bile canaliculi formation and albumin expression. Our results indicate that HepaRG-HB are able to proliferate, self-organize and spontaneously differentiate within the cell culture chambers forming directional bile canaliculi, while HepaRG-HC are observed to aggregate and form tissues resembling 2D HepaRG-HC cultures.