Glomerulus on a chip from iPSC-derived cells: A validation study
This recently published paper from Musah lab at Duke university is a beautiful validation of using kidney on a chip to model glomerular filtration. This tissue chip was lined by epithelial and endothelial cells to mimic the blood filtration barrier and selective molecular filtration function of the kidney. Using this tissue chip, the authors also modeled glomerular injury by administering a clinically relevant dose of the chemotherapy drug Adriamycin.
Results
The results showed the structural integrity disruption of the endothelium and the podocyte tissue layers after drug treatment. Actually, the detachment of dying vascular endothelial cells from the membrane after drug treatment increased the exposure of podocytes to the drug. Hence, they underwent cell injury, characterized by loss of foot processes, retraction of cellular structures, and eventual cell detachment. Afterwards, the authors introduced albumin to the capillary channel and observed a significant increase in the urinary clearance of albumin, confirming the successful recapitulation of drug-induced albuminuria by this chip model.
DigesTable of the paper Roye, Y., et al. (2021). “A personalized glomerulus chip engineered from stem cell-derived epithelium and vascular endothelium.” Micromachines 12(8): 967. 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 an emulate membrane chip. Two microchannels were separated with a porous membrane. The membrane was stretchable to model the dynamics of the pressurized vasculature in the kidney. They used human induced pluripotent stem cell-derived vascular endothelial cells and podocytes from a single patient.
Fabrication: commercially available, Emulate. Inc.
Sterilization: plasma treatment
Cells incorporation: the channels of the chips were flushed with cell culture medium containing the cells
Perfusion/refreshing: continuous perfusion by a pressure driven pump
Treatment: Adriamycin
On-chip read-outs: on-chip monitoring, end-point microscopy
Off-chip read-outs: ELISA
Strong points:
+ Established protocols
+ combination of flow and stretching of the cell layers
+ Long term co-culture of podocytes and endothelial cells
Nothing is perfect! The system can also improve:
– No indication of Adriamycin adsorption/absorption by PDMS
– Operation protocols of the chip do not follow conventional cell culture standards
Conclusion and outlook
This model is useful for personalized medicine purposes. Patient’s biological responses to different therapeutics can be assessed by incorporating individuals’ pluripotent stem cells to the chip.
Contact us if you want to know more about this system or similar technologies!
