Microfluidic Horizons 2026

Study of ADPKD mechanisms in a biomimetic kidney-on-chip

May 18, 2026, 4:40 PM

20m

Oral Organ-on-a-chip and translational models Monday 18/05, 14 - 19; Auditorium

Speaker

Jessica Vandensteen (Institut Curie, Université PSL, Sorbonne Université (Paris, France) - CNRS UMR 168, Physics of Cells and Cancer)

Description

The Autosomal Dominant Polycystic Kidney Disease (ADPKD), is the most common genetic kidney disease, leading to the development of numerous cysts in the renal tubules, and ultimately to kidney failure, without any curative treatment to date. Despite numerous genetic and cell biology studies of ADPKD, the precise mechanism of its cystogenesis, resulting from localized dilation of the renal tubules, remains misunderstood. Our hypothesis is that the mechanical stresses exerted within the tubules play a key role in cyst formation. Our team had developed a kidney-on-chip device in order to mimic the early tubular dilation specific to ADPKD, by using a deformable and tunable extracellular matrix. This microfluidic device enables us to replicate the particular geometry of the tubules and also to decouple flow shear stress and pressure effects on the tubular dilation. We have shown that different pathways can drive the dilation in our in vitro model of ADPKD, depending on the tubular segment studied [1].  In the proximal segment, early tubular dilation is associated with hyperproliferation, while in the collecting duct (mIMCD-3 cells) dilation is linked with a remodeling of the basement membrane and a squamous cell morphology. Moreover, mIMCD-3 tubules are highly sensitive to the extracellular matrix properties and the hydrodynamics constraints encountered. Strickingly, the flow shear stress alone can suppress the dilation specific to ADPKD observed in static condition, while the addition of pressure to this flow shear stress triggers a significant and rapid dilation.  

Ongoing transcriptomics investigations will enable us to identify targets specifically sensitive to flow shear stress or pressure. They already suggest an involvement of genes that contribute to basement membrane remodeling or to the control of cytoskeletal dynamics. Our next step is to use our microfluidic chip to evaluate the effect of disruptive approaches to these key effectors on mimicked tubular dilation [2]. Finally, in a translational approach, we will integrate patient cells within our in vitro kidney tubules to replicate their dilation.

[1] B. Lapin, J. Vandensteen, et al. (2025) Acta Biomaterialia, ISSN 1742-7061, doi: 10.1016/j.actbio.2025.03.022. 

[2] M. Mazloum, B. Lapin, et al. (2024), BioArchiv 597723, doi : 10.1101/2024.06.06.597723.