Adipose-liver on a chip model of NAFLD
A recently published paper from Hesperos Inc./Hickman lab at University of Central Florida co-culturing human hepatocytes and adipocytes representing white adipose tissue. In this multi-organ on a chip different serum-free media formulations were used to represent different human metabolic states.
Results
The system made the crosstalk between liver-on-a-chip and adipose-on-a-chip chambers possible. The authors incorporated adipocyte-hepatocyte interactions in their nonalcoholic fatty liver disease (NAFLD) model. Important aspects of NAFLD progression, including insulin-resistant biomarkers, differential adipokine signaling in different media, and increased TNF-α-induced steatosis were observed in this study.
DigesTable of the paper Slaughter, V. L., et al. (2021). “Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation.” Scientific Reports 11(1): 1-10. 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
2-chamber microfluidic housing contained white adipocyte and hepatocyte modules. Primary human liver cells and Primary human cardiac preadipocytes were used for the aims of this study.
Fabrication: Laser cutting of PDMS and PMMA
Sterilization
Cell incorporation: adipose and hepatocyte coverslips were transferred cell-side up to chambers
Perfusion/refreshing: recirculation with rocker
Treatment: Metformin
On-chip read-outs: live-dead staining, end-point microscopy
Off-chip read-outs: flow cytometry, off-chip imaging, immuno-histo chemistry, ELISA
Strong points:
+Simple technology and rocker perfusion
+ User friendly culture on cover slides
+ Long term culture in different serum free “healthy and diabetic blood-mimetic medium”
Nothing is perfect! The system can also improve:
– Relatively less cellular complexity in liver model
– No indication of drug adsorption/absorption by PMMA and PDMS
– No data for on-chip comparison of hepatocyte phenotype or function with and without adipocytes.
Conclusion and outlook
This adipose-liver model mimics adipocyte-hepatocyte interactions and allows cellular crosstalk. It has the potential to be used for NAFLD and NASH drug development.
Contact us if you want to know more about this system or similar technologies!
