Aim
Renal fibrosis, characterized by the excessive deposition of extracellular matrix proteins, is a driver of progressive chronic kidney diseases. During disease progression, fibrotic lesions replace functional tissue ultimately resulting in organ failure, necessitating the need for renal replacement therapy or renal transplantation. To date, anti-fibrotic therapeutics are hardly available, and drug development is impeded by the lack of appropriate cell and animal models to study human fibrosis. In vitro models lack cellular heterogeneity, which is a prerequisite to mimic the multicellular character of fibrosis, while animal models often do not recapitulate human pathophysiology. To overcome these issues, our lab uses human precision-cut kidney slices (PCKS) to study renal fibrosis and as drug-screening platform.
Method/description
PCKS is a unique model that is more physiologically relevant as compared to most of the currently used in vitro systems. Each slice contains all cell types and acellular components of the whole organ in the original configuration, while preserving cell-cell and cell‐matrix interactions. In other words, PCKS are miniaturized organs that retain native tissue architecture and intact cellular environment, making it an extremely useful model to elucidate the process of fibrogenesis and to accelerate the search for effective anti-fibrotics. In our lab, PCKS are prepared from human renal tissue obtained from either 1) tumor nephrectomies – selecting for macroscopically healthy cortical tissue or 2) end-stage renal disease nephrectomies/transplantectomies. The first group is regarded as healthy and can be used to study the onset of renal fibrosis, while the second group is used to study established fibrosis. In short, PCKS is a useful and versatile translational tool to study renal (patho)physiology.
Collaboration
The project is a collaboration between Departments of Clinical Medicine, Biomedicine, iNANO, Aarhus University, and The Department of Urology, Aarhus University Hospital.
Contact
Associate Professor Rikke Nørregaard, RN@clin.au.dk
Assistant Professor Henricus A.M. Mutsaers, h.a.m.mutsaers@clin.au.dk, Department of Clinical Medicin
Mia Gebauer Madsen, miamadse@rm.dk or www.norregaardlab.com, Department of Clinical Medicine
Anna Krarup Keller, anna.keller@clin.au.dk, Department of Urology
