Flow and vascularization of kidney organoids on a chip

A recent paper by Kim and Chung groups from the Catholic University of Korea culturing vascularized organoids in a kidney on a chip platform and studying the role of shear stress on the formation and nephrotoxicity of the organoids. The authors cultured organoids in a static culture and injected them into the chip. They simulated the shear stress on the organoids for different dimensions of the well and different flow rates using COMSOL Multiphysics software.

Results
The authors found that a coating of 1.5% Matrigel containing 100 ng/mL VEGF overnight was the most effective for the formation of vascularized kidney organoids. Size of organoids was 300-500 µm and the shear stress in the experiments was 1.3e-5 dyne/cm² at 10 µl/min. After treatment with different concentrations of Tacrolimus, a nephrotoxic drug, at different concentrations, they saw lower cell viability in flow conditions compared to the static treatment of the organoids.

Digestible of the paper Lee, H. N., et al. (2021). “Effect of biochemical and biomechanical factors on vascularization of kidney organoid-on-a-chip.” Nano Convergence 8: 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
hPSCs differentiated to kidney organoid on a 24-well plate, then they were and subjected to controlled shear stress in a kidney organoid-on-a-chip platform.
Fabrication method: 3D printing, PDMS molding
Sterilization method: Autoclaving
Organoid incorporation: Organoids were injected into the chip
Perfusion/refreshing method: Syringe pump
On-chip read-outs: On-chip monitoring, Live-dead staining, End-point microscopy
Off-chip read-outs: Off-chip imaging, Immuno-Histo chemistry, Scanning electron microscopy

Strong points:
+ Multiple organoids in one chip
+ Studying the effect of flow on organoids formation and drug toxicity
+ Calculate shear stress on the organoids
+ Vascularized organoids

Nothing is perfect! The system can also improve:
– The same old story, PDMS but no investigation on the real concentration that the organoids are exposed to and what fraction of the drug is absorbed into PDMS
– Using syringe pump decreases the throughput of the experiment although it makes the system simpler
– No evidence that the organoids will enter the wells in the chip

Conclusion and outlook
In this study, the authors suggested that the blood vessel formation from the kidney organoids depends on biochemical and biomechanical stimuli. The effect of biochemical and biomechanical combinatorial stimuli on blood vessel formation needs to be investigated in further studies.

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