Liver pancreas crosstalk in organ on a chip to study type 2 Diabetes

A beautiful paper from Jianhua Qin’s lab from the Chinese Academy of Sciences modelling Liverpancreatic Islet Axis. They used a multi-organoid organ on a chip system to study glucose regulation in physiological and pathological conditions. After culturing the hiPSCs in “micro-wells” and creating embryonic bodies, the authors differentiated them to two lineages of liver and pancreatic islets. Then, they co-cultured these self-assembled differentiated organoids in two different compartments in an organ on a chip and compared liver or islet mono-culture with the co-culture. They performed glucose tolerance test (GTT) to assess glucose utilization.

The authors found out that the co-culture of liver and pancreatic Islets was able regulate glucose consumption and albumin secretion more efficiently compared to the mono-cultures. Moreover, they showed that in hyperglycemic conditions, Metformin treatment restored the respiratory capacity, ATP function and glucose transport functions in both liver and islet organoids. This novel study provides us a unique platform for Type 2 Diabetes mellitus (T2DM) research.

Organ on a chip, Multi-organ microphysiological systems, Microfluidics multi-organ on a chip, organ-organ interaction, iPSC, pancreas, Liver, pancreatic islet, type 2 diabetes

Liver and pancreatic islet organoids were generated from hiPSCs in a micro-well device and were co-cultured in the multi-organoid chip
Fabrication method: Soft lithography and micro-molding with PDMS
Sterilization method: Autoclaving
Cell/organoid incorporation: Liver and islet organoids were injected into the chip device through the liver and islet inlets
Perfusion/refreshment method: Fresh co-culture media was pumped into the chambers by peristaltic pumps
On-chip read-outs:
Live-dead staining, End-point microscopy
Off-chip read-outs: Off-chip imaging (Immuno-Histo chemistry),
Real time-qPCR, ELISA, Flow cytometry

Strong points:
+ Comprehensive differences between co-culture and mono-cultures
+ Using hiPSCs-derived organoids
+ Compartmentalized chip

Nothing is perfect! The system can also improve:
– The same old story, they used PDMS but performed no investigation of the Metformin absorption into PDMS
– Lack of control on the number of organoids cultured in the chip (No data shown)

Conclusion and outlook
In the future, this system may be integrated with other organs such as brain, muscle, and fat to reflect the physiology and pathology of the human body as a whole. It can be used to elucidate the mechanisms and complications associated with metabolic disorders such as insulin resistance, steatohepatitis, etc.

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Link to the paper: https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202103495

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.