Researchers at UTwente and Radboudumc have received a grant for studying fibrotic disease within the Open Technology Programme (OTP) from NOW. The overall aim of the project, called FibOoC is to develop an in vitro human OoC model for fibrotic diseases built from crucial patient-derived cell types, and including essential elements known to drive the disease progression such as dense extracellular matrix, biomechanical cues, and hypoxia. As a case study, we will consider systemic sclerosis as a prototypical fibrotic disease. In this project, we will successively build a generic FibOoC model, generate and characterize patient-specific FibOoC models for systemic sclerosis using cells isolated from patient skin biopsies, and exploit the resulting models, on one hand, to derive disease molecular signatures for diagnosis, prognosis and patient stratification, and on the other hand, to evaluate anti-fibrotic treatments. This project will be conducted in close collaboration between the University of Twente (Prof. Séverine Le Gac) and the Radboudumc (Dr. Wouter Verdurmen, Prof. Peter van der Kraan, Prof. Roland Brock and Dr. Madelon Vonk), with the University of Veterinary Medicine Vienna in Austria as international partner, and several industrial (BEOnChip, Fluigent, Mercurna and Predica Diagnostics) and societal (Proefdiervrij and ReumaNederland) partners.
Left: Schematic representations of skin tissue organizations in healthy and fibrotic contexts, in which abnormal deposition of extracellular matrix (ECM) occurs through excessive synthesis and reduced degradation of the ECM, together with activation of both macrophages and fibroblasts.
Right: Top view of the OoC device in which cells are grown in a 3D hydrogel matrix mimicking the ECM, while being exposed on demand to both mechanical stimulation and soluble factors through the perfusion channel.