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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| http://dx.doi.org/10.1016/j.yexcr.2024.114342 | DOI Listing |
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