NWO Gravitation: Netherlands Organ-on-Chip Initiative
LUMC PI: Prof. Christine Mummery, PhD (Dept. Anatomy)
Start date: 01 October 2017 – End date: 30 September 2028
Cardiovascular, gastrointestinal and brain diseases are major health burdens in developed countries. Without new approaches for prevention and novel therapeutic solutions, these conditions are expected to increase to epidemic proportions in aging populations. The development of new treatments is however hampered by the inability of current model systems to capture features of human tissue and disease. Therefore, it is essential that our traditional methods for health research are redesigned. Human disease-specific stem cell and organoid technologies are increasingly recognized as cutting-edge research platforms for functional genomics, disease modeling and drug target discovery in both academic and commercial sectors. Combined with biophysical and biochemical assays, multicellular microfluidic structures, they are already accelerating drug repurposing and supporting drug target discovery. NOCI aims to develop these new approaches, designated as â??Organ-on-chipâ??, and achieve a paradigm shift from empirical treatment of symptoms of disease to cures based on correcting the underlying cause. The six main applicants are internationally leading scientists and physicians in the diverse fields of stem cell biology, microfluidics engineering, microbiota and systems genetics and pathophysiology of cardiovascular, neural and intestinal disease. They have already established collaborations through the Institute for Human Organ and Disease Model Technologies (hDMT), founded to co-develop Organs-on-chip. Our mission is (i)to make complex human tissue and organ systems in Organ-on-chip devices that model cardiovascular, brain and gastrointestinal diseases; (ii)provide readouts of disease pathology as diagnostic, disease-state and therapeutic response biomarkers; (iii)integrate the human (intestinal) microbiome and inflammatory component of disease into chips; (iv)use the models to identify/engineer disease mutations, genetic modifiers and variants predisposing to disease for prevention, personalized medicine and new therapeutics; (v)replace/reduce animal experiments. NOCI involves three Scientific Challenges: (S1) mastering human stem cell and organoid biology in complex multicellular structures for Organ-on-chip formats; (S2) mastering biomarker resolution in monitoring disease; (S3) mastering non-invasive methods to monitor signal transduction, gene expression and epigenetic regulation. Each challenge focuses on fundamental questions regarding cells, disease pathology, its confounders, and materials and formats of microfluidic devices that capture the biomechanics, biochemistry and molecular biology of the tissue niche. This multidisciplinary approach will result in better understanding of human tissue biology and disease, communication between tissue cells, blood vessels, (body) fluids and component cytokines and hormones, biomaterials and the microbiome, and the effects of genetic variants and mutations. The resulting knowledge, experimental tools and disease models will be integrated into three Technological Challenges covering the Organ-on-chip process, specifically: (T1) chip design and production, including controlled biomechanics, biochemistry and fluid flow; (T2) integration of stem cells and organoids; (T3) relevant biomarkers as readout of the disease. Through our existing links with the pharmaceutical sector (in part through hDMT), we will showcase the usability of complex human tissue models for screening new treatments and repurposing existing drugs. This is at the heart of human stem cell-, organoid- and Organs-on-chip research in the Netherlands. We expect our program to impact Dutch biomedical research beyond the diseases used as exemplars and the decade for which the work is planned.