An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture.
Primary hepatocytes represent a physiologically relevant model for drug toxicity screening. Here, we created a biologically inspired artificial liver sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the liver acinus. This unit consisted of a cord of hepatocytes (50 x 30 x 500 microm) fed by diffusion of nutrients across the microfluidic endothelial-like barrier from a convective transport vessel (10 nL/min). This configuration sustained rat and human hepatocytes for 7 days without an extracellular matrix (ECM) coating. Experiments with the metabolism mediated liver toxicant diclofenac showed no hepatotoxicity after 4 h and an IC(50) of 334 +/- 41 microM after 24 h.
Lee
Philip J
PJ
Department of Bioengineering, Biomolecular Nanotechnology Center, Berkeley Sensor and Actuator Center, University of California-Berkeley, Berkeley, CA 94720-1762, USA.
Hung
Paul J
PJ
Lee
Luke P
LP
D000818:Animals; D032701:Biomimetics / Q000295:instrumentation* / Q000379:methods; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D008102:Liver Circulation / Q000502:physiology; D019164:Liver, Artificial; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D051381:Rats; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods