Next generation in vitro models for combating polycystic kidney disease

An hiPSC-based fluorescent reporter imaging platform for drug discovery to combat polycystic kidney disease, KIDNEY3D

Leiden University together with the company OcellO will establish polycystic kidney disease (PKD) disease model systems that integrate biomarkers for PKD disease initiation and progression, allowing advanced drug discovery.

PKD accounts for around 1 in 10 of all people undergoing a kidney transplant or dialysis, corresponding to approximately 50,000 people across Europe. Without dialysis or transplantation, kidney failure due to PKD is life-threatening. However, neither dialysis nor transplantation is a cure for PKD. A pharmacological intervention that would arrest PKD progression and prevent kidney failure is highly desired by patients and healthcare providers.

The project aims to develop improved patient relevant test systems that will help identifying and validate promising drug candidates faster and cheaper. This would have major impact on the quality of life of PKD patients and their continuous contribution to society.

The consortium will use bioinformatics approaches to uncover relevant disease biomarkers based on signalling networks that trigger disease onset and progression. We will use genetically engineered human induced pluripotent stem cells (hiPSC) carrying a PKD1 mutation that can be differentiated to kidney organoids. Wild-type and PKD1 mutant hiPSC cells will be genetically modified to express fluorescent protein markers of disease triggering and progression. These hiPSC reporters will be differentiated into renal epithelial cells as well as kidney organoids and evaluated for implementation in advanced microscopy settings to derive temporal quantitative information on disease biomarker activation. The main deliverable of this project is to establish PKD models with integrated biomarkers for disease initiation and progression, that can ultimately be used for imaging-based drug discovery.

Polycystic kidney disease is a critical chronic disease that limits patients to actively participate in society and still lacks successful treatments. To combat this disease, the consortium will use genetically engineered human induced pluripotent stem cell reporter lines which can be differentiated into kidney organoids and used for imaging-based drug discovery.
Technology Readiness Level (TRL)
2 - 3
Time period
24 months