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Tissue Engineering

Tissue Engineering - Poster Session D

Poster BB16 - A Perfusable Human Collecting Duct-on-Chip Model

Friday, October 25, 2024
3:30 PM - 4:30 PM EST
Location: Exhibit Hall E, F & G

Introduction:  In human kidneys, the collecting duct is central for urine modification and drainage and is often subject to disease and dysfunction. Perfusable in vitro models of the collecting duct could expedite drug testing and disease modeling. However, existing models are currently limited by the availability of appropriate human cell lines or lack of relevant biophysical cues such as flow. The recent development of protocols to derive ureteric bud (UB) and collecting duct (CD) organoids from human induced pluripotent stem cells (hiPSCs) provides an opportunity to advance in vitro models. Here, we aim to develop perfusable models of the ureteric bud and collecting duct from hPSCs.

Materials and

Methods:  Building upon our prior proximal tubule-on-chip models, we created UB organoids, dissociated them into single cells, and then seeded these cells in a 3D channel to form a confluent monolayer surrounded by extracellular matrix (ECM). By optimizing the ECM composition to include collagen I, we could longitudinally perfuse our UB-on-chip model, while maintaining UB cell phenotype and morphology over several days to weeks.

Results, Conclusions, and Discussions: We found that UB cells form a perfusable lumen consisting of an epithelial monolayer that can bud into the surrounding ECM akin to branching morphogenesis observed in developing embryonic kidneys. Ongoing work is focused on understanding the effects of flow on UB maturation and function as well as further differentiating the UB epithelium to generate a human collecting duct model.

Acknowledgements (Optional):