Hepatic cord like structure in a liver on a chip using HepaRG cell line

A recent paper from Le Pioufle lab at CNRS France modelling the microstructure of the hepatic cord within the liver by confining hepatocytes in tiny hepatic-cord like chambers in a liver on a chip system. These chambers are in contact with another channel containing various media through tiny slits with controlled dimensions.

Results
The authors seed proliferative hepatoblast-like HepaRG cell lines at low density into the chip and differentiate them in the chip with the help of DMSO containing medium in the medium microchannel. Finally, they tested different concentrations of Acetaminophen to study the hepato-toxicity of the drug on the cells. It was observed that HepaRG hepatocytes in this platform were responsive to Acetaminophen exposure and their viability was significantly reduced after treatment.

Digestible of the paper Boul, M., et al. (2021). “A versatile microfluidic tool for the 3D culture of HepaRG cells seeded at various stages of differentiation.” Scientific Reports 11(1): 14075. This paper is reproduced under https://creativecommons.org/licenses/by/4.0/. The image of the chip was edited for better clarity, data in the table and text were compiled and interpreted by AZAR Innovations.

Method
The authors used a microfluidic device which comprised a medium flowing channel and a cell loading, channel (containing human HepaRG cells) which were interconnected via slits
Fabrication method: Soft lithography with PDMS
Sterilization method: 70% ethanol, Autoclaving
Cell incorporation: Cells were sucked into the channel by negative pressure in the outlet
Perfusion/refreshing method: Constant flow rate by a syringe pump
On-chip read-outs: On-chip monitoring, End-point microscopy, Live-dead staining
Off-chip read-outs: ELISA

Strong points:
+ Mimicking structure of hepatic cord
+ Controlled differentiation of the cells
+ Different designs of the connecting slits
+ Simulations to know the flow within the channels

Nothing is perfect! The system can also improve:
– The same old story, PDMS but no investigation on the real concentration of the drugs
– Using cell lines
– Medium was not in contact with the incubator condition, rather it was in a closed syringe before coming into contact with the cells.
– Long tubing was used.

Conclusion and outlook
In this novel platform, hepatocytes take on a 3D organization and can be cultured under flow perfusion for the long term. It can be used as a new platform for drug toxicity assays with hepatocytes from different sources.

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