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The collecting duct is the last segment of the kidney nephron and plays a vital role in fine-tuning urine composition. The complex physiology of the collecting duct is still not completely understood. Here, more advanced cell models are required to help solve these unanswered questions.
To this end, researchers Charlotte Olde Hanhof, Emre Dilmen, Idil Orhon and Joost Hoenderop from the department of Medical BioSciences developed a mouse tubuloid model that could be used to study collecting duct function. This model resulted from a close collaboration with the group of Marianne Verhaar of the department of Nephrology and Hypertension in the University Medical Centre Utrecht. The results were published in the journal of Frontiers in Cell and Developmental Biology on 25 January 2023.
Tubuloids are an advanced three-dimensional in vitro cell culture model, as can be seen in the picture of this newsletter, and can be grown directly from kidney or urine material. Tubuloids contain cells of almost all of the segments of the nephron, including the proximal tubule and more distal segments like the collecting duct. Still, tubuloids remain in an immature state with the current culture protocol and further maturation is needed to prepare for functional analysis. In the current manuscript, the researchers describe a novel mouse tubuloid culture protocol that leads to increased collecting duct maturation and function. Multiple methods including fluorescence microscopy were employed to show increased maturation in mouse tubuloids as they expressed multiple collecting duct markers on RNA and protein level. Also, tubuloids responded to physiologic relevant factors for the collecting duct. Finally, functional studies with radioactive sodium demonstrated, for the first time ever, collecting duct-specific sodium uptake in a tubuloid model.
This study shows that mouse tubuloids can be used to model the collecting duct physiology. A major advantage of mouse tubuloids is that they can be easily grown from existing (disease) mouse models. This might reduce the need for additional mouse experiments and may provide new insights into collecting duct function in health and disease in the future.
Read the study here: Olde Hanhof CJA, Dilmen E, Yousef Yengej FA, Latta F, Ammerlaan CME, Schreurs J, Hooijmaijers L, Jansen J, Rookmaaker MB, Orhon I, Verhaar MC, Hoenderop JG. Differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiology. Front Cell Dev Biol. 2023 Jan 25;11:1086823. doi: 10.3389/fcell.2023.1086823. PMID: 36760360; PMCID: PMC9905633.
