Development of high-throughput platforms for human kidney disease modeling
Novel human in vitro model systems for kidney diseases are urgently needed since data from rodent models is often not transferable to humans. Furthermore, in vitro platforms can be scaled-up toward true high-throughput and thus will advance target discovery and validation, as well as drug screening studies. In this project, we will develop novel in vitro model systems having three main goals in mind.
1) The development of a macroscopic model of a perfused human kidney tubule to model adult polycystic kidney disease.
2) The design of a real resolution kidney system using rod shaped microgels with a scalable diameter of 8-200 µm for Anisogel alignment with the aim to develop a model of kidney fibrosis.
3) Our final aim is to move the system towards true high-throughput disease modeling and we will achieve this using automated pipetting and analysis methods, including novel bioprinting techniques.
Therefore, we will design synthetic polyethylene glycol (PEG)-based bioinks, consisting of rod-shaped, magneto-responsive microgels, to model the human tubulo-interstitium. We will compare these in vitro platforms with human kidney disease specimen and donor biopsies using scRNA-sequencing with the goal to have a model that reflects human disease.
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Rommel D, Mork M, Vedaraman S, Bastard C, Guerzoni LPB, Kayku Y, Vinokur R, Born N, Haraszti T, De Laporte L. Functionalized microgel rods crosslinked into soft macroporous structures for 3D cell culture. Advanced Sciences 2022, e2103554.