Development of the liver lobule-type culture device

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We have developed devices made of silicon for the co-culture of rat small hepatocytes (SHs) and biliary epithelial cells (BECs). Cells could proliferate and survive on a silicon-device that oxygen freely passes through. We coated channels of the silicon-device with various ECM to examine their effects on morphogenesis. However, we have not found an optimal condition for that bile ducts (BDs) reconstructed by BECs connect to bile canaliculi of hepatic organoids reconstructed by matured SHs. By using microfluidic platform, we analyzed angiogenesis in 3D cultures in which collagen gel separated rat mature hepatocytes and endothelial cells (ECs), and found that ECs formed vascular sprouts in collagen gels. Laminins 111 and 521 were necessary for hepatic progenitor cells to differentiate into BECs and to form mature duct structures, respectively. A transcription factor Grhl2 enhanced the morphogenesis of BDs by regulating the expression and the location of claudins 3 and 4.