Drug discovery is oftentimes hindered by inadequate disease models. For diseases affecting the liver 2D hepatocyte culture models are generally used which fail to recapitulate the organ functions and pathophysiologies. Organ-on-a-chip technique has recently gained attention for liver modeling, and several devices containing different liver cell types have been developed. The present invention is a liver-on-a-chip (LoC) device which contains hepatocytes and cholangiocytes (bile duct epithelial cells) therefore reproducing the hepatic region around the bile duct in 3D for the first time.
Technical Summary
The inventors developed a PDMS microfluidic device with two parallel microchannels separated by two PET membranes (Fig.1A). Hepatocytes are placed into the top channel and the bottom channel is seeded with either cholangiocytes or endothelial cells to reproduce the hepatic region around the bile duct (ibd-LoC) or blood vessels (bv-LoC) respectively (Fig. 1B).
➤ Tubular bile duct-like structure is formed
The inventors have shown that the manufactured device can be used to obtain a tubular bile duct-like structure to accurately mimic the pathophysiology of the liver around the bile ducts. Previous attempts at reproducing tubular bile duct structures
in vitro failed due to a technical difficulty of low migration rate of bile duct epithelial cells. The present device faithfully reproduces bile duct structure allowing the assessment of bile acid kinetics.
➤ Drug screening can be performed
PDMS microfluidic devices pose a concern of drug absorption which might hinder their utility for drug screening. The inventors developed a method to estimate drug-specific absorption of the device which shows that only drugs with high S + log D values are absorbed (Deguchi et al. 2021). They then applied several low S + log D drugs and confirmed that the device can successfully be used for small molecule drug screening (Deguchi et al. 2023).
Current development status
Microfluidic device has been verified to be effective for modeling liver pathophysiology in COVID-19 and testing antiviral and immunosuppressive drugs
Applications
Intellectual Property
Kyoto University was founded in 1897, the second university to be established in Japan. Kyoto University is among 10 National Designated Universities in Japan. It boasts 18 graduate schools, 10 faculties, 12 research institutes, and 26 centers and other establishments. Research conducted at Kyoto University spans the full spectrum of fields from social to natural science.
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