Project Details
Projekt
Advanced ex vivo human kidney disease models using induced pluripotent stem cells
Subject Area
Nephrology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 445703531
Chronic kidney disease (CKD) affects more than 10% of the world population. While there are some novel therapies available, the majority of patients still progress towards end-stage kidney disease (ESKD). Drugs and targets discovered in murine models and simplistic 2D model systems that do not represent human disease conditions lead to high attrition rates in clinical trials. To mitigate this failure risk caused by lack of efficacy and side-effects, reduce animal use, and make drug discovery more cost efficient, well-characterized 3D models that mimic the complex pathophysiology of kidney diseases are needed. While induced pluripotent stem cell (iPSC)-derived kidney organoids have progressed, they primarily represent early developmental stages of human kidneys, and are difficult to standardize with many off-target cell-types. Thus, a more standardizable and scalable system is needed that allows to model complex cellular interactions that drive kidney disease. In the first funding period, we developed novel tissue engineering and disease modelling tools for the kidney focused on adult cells and cell-lines together with novel biomaterials and bioprinting methods. While we could demonstrate that for certain diseases such as polycystic kidney disease using primary cells is an advantage more complex cellular architectures are needed for most other diseases. Therefore, we hypothesize that a combination of induced pluripotent stem cells (iPSC) differentiation and bioengineering approaches will allow us to more precisely model human kidney tissue in homeostasis and disease. In this project, in WP1 we will utilize the combined expertise of a chemical engineer (De Laporte) and a kidney disease expert (Kramann) to develop macroporous hydrogel systems via microgel assembly for combined iPSC expansion and differentiation into kidney tissue within the biomaterial construct. In WP2 we will test various injury models in this system and compare them together with P2, P3 and P8 to human disease using advanced single cell and spatial OMICs to identify a system that largely reflects human pathophysiology. In WP3 we will increase the standardization and throughput of this technology using an automated pipetting and 3D imaging system to perform compound screening based on computationally selected targets with the ultimate goal to validate novel targets for the vast and growing patient population suffering from CKD.
DFG Programme
Clinical Research Units
