Liver sinusoid is the main functional site in liver. Multiple types of hepatic cells are well organized in a precisely-controlled biochemical and biomechanical environment, maintaining a spectrum of hepatic functions. Here, using micro-engineering techniques, four types of primary hepatic cells are integrated into two layer channels connected by porous membrane, which recreates the sinusoidal cell composition and architecture. By incorporating shear flow into this permeable system, the blood flow in sinusoids and interstitial flow in space of Disse are recapitulated. Conventional hepatocyte-based liver-specific functions are enhanced by non-parenchymal cells co-culture and shear flow. Moreover, major immune responses in liver sinusoids, i.e., neutrophil recruitment under lipopolysaccharide (LPS) stimulation, are replicated, indicating that all types of hepatic cells contribute to this process. Thus, this liver chip provides a new in vitro model to investigate the short-duration cellular interactions under a microenvironment mimicking the physiological composition and architecture of liver organ.
Keywords: Co-culture; Hepatic cells; Liver sinusoid chip; Microfluidic; Shear flow.
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