Test animals, hold your breath

Human iPSCs at the heart of renal model chip development
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Release content has been edited for accuracy. [4 July 2023]

Kyoto, Japan -- Animal experimentation may not be a thing of the past just yet, but work on human iPS cell technology may someday grant emancipation for lab mice and other species.

Renal proximal tubules play a major role in our kidneys' ability to reabsorb vital substances into the bloodstream, such as albumin, before the conversion to urine.

However, in order to pursue accurate testing and other applications, researchers have needed a quantitative evaluation system that simulates the function of these tubules; existing methods could only evaluate epithelial cells using animal experiments and cultures.

A team of researchers from Kyoto University has now developed a model microchip using human iPS cells to measure the transport capacity of the membrane proteins and potentially give test animals some respite.

"We focused on the fact that human iPSC-derived organoids contain highly functional cells whose functions are enhanced when cultured on a microfluidic device," explains the lead author Ramin Banan Sadeghian of KyotoU's Graduate School of Engineering.

This microphysiological system -- or MPS -- is designed to reproduce the mechanisms of glucose reabsorption and drug excretion in the renal proximal tubules in vitro and ex vivo, mimicking the function of human epithelial tissue.

"We found that glucose uptake and transport are at significantly higher rates through the engineered co-culture tissue than through monocultures," reveals team leader Ryuji Yokokawa at KyotoU's Department of Micro Engineering, referring to the team's use of a blend of pluripotent cell-derived and immortalized proximal tubule epithelial cells.

"Our results also showed that shear stress stimulation of the two cell types increased the transport capacities of the membrane proteins SGLT-2 and P-gp," add co-author Minoru Takasato at RIKEN Center for Biosystems Dynamics Research and Toshikazu Araoka at KyotoU's Center for iPS Cell Research and Application.

Yokokawa's team anticipates applying their MPS model as a screening tool for developing new drugs by evaluating the transport and nephrotoxicity of various membrane proteins.

For example, these methods may enable patient-specific disease modeling, drug screening, and pathogenesis study by incorporating patient-derived stem cells into the required organoids.

"Our MPS model will allow us to incorporate patient-derived stem cells that will enable personalized medicine studies," notes Yokokawa.

Caption: The first hybrid kidney tubule on a chip: Human iPSC-derived kidney organoid with endothelial cells set on a microchip
Credit: KyotoU/Jake Tobiyama
Ramin, Banan-sadeghian
Toshikazu Araoka