Chronic inflammatory diseases affect millions of Canadians and thousands of Albertans, and incur huge costs to the health care system and patient quality of life. Many chronic inflammatory diseases involve a failure of epithelial barrier systems that separate the external environment from the internal milieu of our bodies. It is also becoming apparent that aberrant interactions between the microbiota and intestinal epithelium contribute to chronic inflammatory diseases beyond the gut (e.g. psoriasis, rheumatoid arthritis, diabetes, obesity, allergy). The study of the underlying pathophysiology and the development of new treatments has been slowed by our reliance on animal models or cancer cell lines, which fail to accurately reflect the human disease state. The ability to study a patient’s own cells, in concert with their unique intestinal microbiota, and to use these to test new therapies, would vastly improve the “idea to lab to clinic” pipeline. For example, in the inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, a failure of the epithelial barrier to prevent the commensal bacteria in the lumen of the gut from entering the intestinal wall, leads to a chronic tissue-damaging immune and inflammatory reaction in susceptible individuals. Furthermore, the critical roles of the epithelium as the key interface between the intestinal microbiota and the body, and as a major site of drug metabolism, further suggest that the development of new therapies to re-establish and maintain the epithelial barrier could be of immense benefit to patients.
New technology has recently been developed that allows the isolation of patient-derived intestinal stem cells to generate epithelial cell cultures and establish epithelial barrier structures in the lab that closely model the biology of the human intestinal epithelium. These so-called “organoids” represent the forefront of research into chronic inflammatory diseases, and provide the ideal platform for patient-oriented fundamental research initiatives to support the implementation of personalized medicine. We have established a new Human Tissue Research Platform to grow patient biopsies as organoids in order to simultaneously characterize individual patient biology, as well as test new therapeutic strategies.
This platform will take advantage of the University of Calgary’s Intestinal Inflammation Tissue Bank (IITB), located within the Snyder Institute for Chronic Diseases, which is a well-established and continuously growing human biobank containing more than 6000 human tissue, blood, stool, and urine samples, more than 600 of which have also been genetically characterized. Our multi-disciplinary team will use this innovative, translational research platform, which expands the functionality of the IITB, along with additional existing infrastructure and core facilities, to:
1) Facilitate patient tissue-based studies to address key questions in disease etiology.
2) Provide high-throughput screening capability to attract investment and interaction with biotech and pharma.
3) Establish a state-of-the-art training facility that will add to Alberta’s highly skilled workforce and promote economic diversity in the health research/biotech/health care sector. The team is led by nationally recognized researchers in epithelial biology and chronic inflammatory disease.
Our team at the University of Calgary is developing a state-of-the-art Human Tissue Research Platform that will allow researchers throughout Alberta and Canada to study the epithelial barrier in model systems established using fresh or cryogenically preserved biopsy samples from well-characterized patients, as well as interactions with other biological compartments, such as the immune system (e.g. blood-derived immune cells), the submucosal support system (e.g. fibroblasts and associated extracellular stromal tissues), and the intestinal microbiota (e.g. stool-derived bacteria and/or bacterial components) in a patient-matched manner. Our platform will become a hub that draws on patient samples obtained through the University of Calgary’s Intestinal Inflammation Tissue Bank (IITB). Standard patient data will be combined with individualized genomic (University of Calgary Genomics Centre), metabolomics (Calgary Metabolomics Research Facility – CMRF), proteomics/peptidomics (Southern Alberta Mass Spectrometry – SAMS Facility) and microbiome (International Microbiome Centre) data. Thus, we will be uniquely positioned to study pathobiology in individual patients, each with a defined “omics” signature, and will be uniquely positioned in Canada as the only platform that can facilitate “personalized science driving personalized medicine”.