New microphysiological system mimics human kidney function

Animal experimentation remains a prevalent practice, but advancements in human induced pluripotent stem cell (iPSC) technology offer hope for the liberation of laboratory animals in the future. The renal proximal tubules play a crucial role in the kidneys’ ability to reabsorb vital substances, such as albumin, into the bloodstream before their conversion to urine.

To conduct accurate testing and other applications, researchers have sought a quantitative evaluation system that simulates the function of these tubules. Previous methods relied on animal experiments and cultures to assess epithelial cells, but a team of researchers from Kyoto University has now developed a model microchip utilizing human iPSCs to measure the transport capacity of membrane proteins. This breakthrough could potentially provide relief for test animals. The research paper titled “Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule” was published in Communications Biology.

Lead author Ramin Banan Sadeghian from Kyoto University’s Graduate School of Engineering explains, “We focused on the fact that human iPSC-derived organoids contain highly functional cells whose functions are enhanced when cultured on a microfluidic device.”

This microphysiological system, known as MPS, aims to replicate the mechanisms of glucose reabsorption and drug excretion in the renal proximal tubules both in vitro and ex vivo, mirroring human epithelial cells.

Toshikazu Araoka from Kyoto University’s Center for iPS Cell Research and Application (CiRA) states, “We found that glucose uptake and transport occur at significantly higher rates through the engineered co-culture tissue than through monocultures.” The team achieved this by utilizing a combination of pluripotent cell-derived and immortalized proximal tubule epithelial cells.

Team leader Minoru Takasato from the RIKEN Center for Frontier Biosciences adds, “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.”

The team, led by Takashi Yokokawa, envisions applying their MPS model as a screening tool for newly developed drugs. This would involve evaluating the transport and nephrotoxicity of various membrane proteins. Additionally, these methods could facilitate patient-specific disease modeling, drug screening, and pathogenesis studies by incorporating stem cells derived from patients into the necessary organoids.

Yokokawa emphasizes, “Our model will enable us to obtain diseased cells that can be co-cultured with existing cell lines to form a homogenous tissue for analysis and treatment purposes.”

Source: Kyoto University

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