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Enhanced podocyte differentiation and changing drug toxicity sensitivity through pressure-controlled mechanical filtration stress on a glomerulus-on-a-chip.

  • Doi, Kotaro1
  • Kimura, Hiroshi2
  • Kim, Soo Hyeon1
  • Kaneda, Shohei3
  • Wada, Takehiko4
  • Tanaka, Tetsuhiro5
  • Shimizu, Akira6
  • Sano, Takanori1
  • Chikamori, Masamichi1
  • Shinohara, Marie1
  • Matsunaga, Yukiko T1
  • Nangaku, Masaomi7
  • Fujii, Teruo8
  • 1 Institute of Industrial Science, The University of Tokyo, Tokyo, Japan. , (Japan)
  • 2 Micro/Nano Technology Center, Tokai University, Kanagawa, Japan. , (Japan)
  • 3 Department of Mechanical Systems Engineering, Faculty of Engineering, Kogakuin University, Tokyo, Japan. , (Japan)
  • 4 Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Kanagawa, Japan. , (Japan)
  • 5 Department of Nephrology, Rheumatology and Endocrinology, Tohoku University Graduate School of Medicine, Miyagi, Japan. , (Japan)
  • 6 Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan. , (Japan)
  • 7 Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. , (Japan)
  • 8 The University of Tokyo, Tokyo, Japan. [email protected]. , (Japan)
Published Article
Lab on a Chip
The Royal Society of Chemistry
Publication Date
Dec 22, 2022
DOI: 10.1039/d2lc00941b
PMID: 36546862


Podocytes, localized in the glomerulus, are a prognostic factor of proteinuria in kidney disease and are exposed to distinct physiological stimuli from basal to apical filtration flow. Research studies on drug discovery and disease modeling for glomerulopathy have developed a glomerulus-on-a-chip and studied podocyte mechanobiology to realize alternative methods to animal experiments. However, the effect of filtration stimulus on podocytes has remained unclear. Herein, we report the successful development of a user-friendly filtration culture device and system that can precisely control the filtration flow using air pressure control by incorporating a commercially available culture insert. It allows mouse podocytes to be cultured under filtration conditions for three days with a guarantee of maintaining the integrity of the podocyte layer. Using our system, this study demonstrated that podocyte damage caused by hyperfiltration resulting from glomerular hypertension, a common pathophysiology of many glomerulopathies, was successfully recapitulated and that filtration stimulus promotes the maturation of podocytes in terms of their morphology and gene expression. Furthermore, we demonstrated that filtration stimulus induced different drug responsiveness in podocytes than those seen under static conditions, and that the difference in drug responsiveness was dependent on the pharmacological mechanism. Overall, this study has revealed differentiating and pharmacodynamic properties of filtration stimulus and brings new insights into the research field of podocyte mechanobiology towards the realization of glomerulus-on-a-chip.

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