A semi-permeable insert culture model for the distal part of the nephron with human and mouse tubuloid epithelial cells

E Dilmen; C J A Olde Hanhof; F A Yousef Yengej; C M E Ammerlaan; M B Rookmaaker; I Orhon; J Jansen; M C Verhaar; J G Hoenderop

doi:10.1016/j.yexcr.2024.114342

A semi-permeable insert culture model for the distal part of the nephron with human and mouse tubuloid epithelial cells

E Dilmen, C J A Olde Hanhof, F A Yousef Yengej, C M E Ammerlaan, M B Rookmaaker, I Orhon, J Jansen, M C Verhaar, J G Hoenderop^*

^*Corresponding author for this work

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Abstract

Tubuloids are advanced in vitro models obtained from adult human or mouse kidney cells with great potential for modelling kidney function in health and disease. Here, we developed a polarized human and mouse tubuloid epithelium on cell culture inserts, namely Transwell™ filters, as a model of the distal nephron with an accessible apical and basolateral side that allow for characterization of epithelial properties such as leak-tightness and epithelial resistance. Tubuloids formed a leak-tight and confluent epithelium on Transwells™ and the human tubuloids were differentiated towards the distal part of the nephron. Differentiation induced a significant upregulation of mRNA and protein expression of crucial segment transporters/channels NKCC2 (thick ascending limb of the loop of Henle), NCC (distal convoluted tubule), AQP2 (connecting tubule and collecting duct) and Na +/K +-ATPase (all segments) in a polarized fashion. In conclusion, this study illustrates the potential of human and mouse tubuloid epithelium on Transwells™ for studies of tubuloid epithelium formation and tubuloid differentiation towards the distal nephron. This approach holds great promise for assisting future research towards kidney (patho)physiology and transport function.

Original language	English
Article number	114342
Journal	Experimental Cell Research
Volume	444
Issue number	1
Early online date	18 Nov 2024
DOIs	https://doi.org/10.1016/j.yexcr.2024.114342
Publication status	Published - 1 Jan 2025

Keywords

Epithelium
Kidney
Organoids
Stem cell
Tubuloids

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10.1016/j.yexcr.2024.114342Licence: CC BY

1-s2.0-S0014482724004336-mainFinal published version, 6.89 MBLicence: CC BY

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Dilmen, E., Olde Hanhof, C. J. A., Yousef Yengej, F. A., Ammerlaan, C. M. E., Rookmaaker, M. B., Orhon, I., Jansen, J., Verhaar, M. C., & Hoenderop, J. G. (2025). A semi-permeable insert culture model for the distal part of the nephron with human and mouse tubuloid epithelial cells. Experimental Cell Research, 444(1), Article 114342. https://doi.org/10.1016/j.yexcr.2024.114342

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abstract = "Tubuloids are advanced in vitro models obtained from adult human or mouse kidney cells with great potential for modelling kidney function in health and disease. Here, we developed a polarized human and mouse tubuloid epithelium on cell culture inserts, namely Transwell{\texttrademark} filters, as a model of the distal nephron with an accessible apical and basolateral side that allow for characterization of epithelial properties such as leak-tightness and epithelial resistance. Tubuloids formed a leak-tight and confluent epithelium on Transwells{\texttrademark} and the human tubuloids were differentiated towards the distal part of the nephron. Differentiation induced a significant upregulation of mRNA and protein expression of crucial segment transporters/channels NKCC2 (thick ascending limb of the loop of Henle), NCC (distal convoluted tubule), AQP2 (connecting tubule and collecting duct) and Na +/K +-ATPase (all segments) in a polarized fashion. In conclusion, this study illustrates the potential of human and mouse tubuloid epithelium on Transwells{\texttrademark} for studies of tubuloid epithelium formation and tubuloid differentiation towards the distal nephron. This approach holds great promise for assisting future research towards kidney (patho)physiology and transport function. ",

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AU - Olde Hanhof, C J A

AU - Yousef Yengej, F A

AU - Ammerlaan, C M E

AU - Rookmaaker, M B

AU - Orhon, I

AU - Jansen, J

AU - Verhaar, M C

AU - Hoenderop, J G

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N2 - Tubuloids are advanced in vitro models obtained from adult human or mouse kidney cells with great potential for modelling kidney function in health and disease. Here, we developed a polarized human and mouse tubuloid epithelium on cell culture inserts, namely Transwell™ filters, as a model of the distal nephron with an accessible apical and basolateral side that allow for characterization of epithelial properties such as leak-tightness and epithelial resistance. Tubuloids formed a leak-tight and confluent epithelium on Transwells™ and the human tubuloids were differentiated towards the distal part of the nephron. Differentiation induced a significant upregulation of mRNA and protein expression of crucial segment transporters/channels NKCC2 (thick ascending limb of the loop of Henle), NCC (distal convoluted tubule), AQP2 (connecting tubule and collecting duct) and Na +/K +-ATPase (all segments) in a polarized fashion. In conclusion, this study illustrates the potential of human and mouse tubuloid epithelium on Transwells™ for studies of tubuloid epithelium formation and tubuloid differentiation towards the distal nephron. This approach holds great promise for assisting future research towards kidney (patho)physiology and transport function.

AB - Tubuloids are advanced in vitro models obtained from adult human or mouse kidney cells with great potential for modelling kidney function in health and disease. Here, we developed a polarized human and mouse tubuloid epithelium on cell culture inserts, namely Transwell™ filters, as a model of the distal nephron with an accessible apical and basolateral side that allow for characterization of epithelial properties such as leak-tightness and epithelial resistance. Tubuloids formed a leak-tight and confluent epithelium on Transwells™ and the human tubuloids were differentiated towards the distal part of the nephron. Differentiation induced a significant upregulation of mRNA and protein expression of crucial segment transporters/channels NKCC2 (thick ascending limb of the loop of Henle), NCC (distal convoluted tubule), AQP2 (connecting tubule and collecting duct) and Na +/K +-ATPase (all segments) in a polarized fashion. In conclusion, this study illustrates the potential of human and mouse tubuloid epithelium on Transwells™ for studies of tubuloid epithelium formation and tubuloid differentiation towards the distal nephron. This approach holds great promise for assisting future research towards kidney (patho)physiology and transport function.

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A semi-permeable insert culture model for the distal part of the nephron with human and mouse tubuloid epithelial cells

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