Mesenchymal stem cell-derived liver-on-a-chip reconstitutes human liver structure and function.

Abstract

An in vitro model of human liver with functional integrity would advance liver research and enable personalized therapeutics. A microfluidic liver-on-a-chip can generate a functional hepatobiliary network using human liver cells and recapitulate blood circulation and bile excretion. However, many current microfluidic liver models lack a biliary component and cannot fully recapitulate the excretory function of the human liver. Here, we develop a microfluidic liver-on-a-chip incorporating functional endothelial cells, hepatocytes, and cholangiocytes derived from a single source of human mesenchymal stem cells. This stem cell-derived liver-on-a-chip reconstructs a simplified liver unit, including a sinusoid, a hepatocyte compartment, and a bile duct supported by barrier integrity and fluid flow. It reproduces integrated organ-level responses to xenobiotics, including hepatic uptake and biliary excretion, and models ischemic liver injury with therapeutic cell recruitment. This technology expands personalized organ-level modeling and holds strong potential for studying tissue development and advancing targeted therapies for liver injury.