Stromal cells biology in intestinal fibrosis; the role of myofibroblast

Speaker: Professor George Kolios - Democritus University of Thrace, Alexandroupolis, Greece

Abstract: Stromal cells are abundant in the intestinal wall and together with the extracellular matrix (ECM) constitute the connective tissue of the gut. Besides their structural role there are accumulating evidence that stromal cells participate in host defense, autoimmune intestinal inflammation, epithelial reinstitution, wound healing and the maintenance of intestinal homeostasis. During chronic intestinal inflammation stromal cells respond to the local cytokine milieu in cooperation with extracellular matrix components to regulate the process of wound healing or to induce intestinal fibrosis. Post-inflammatory scarring represents a failure to effectively remodel ECM and achieve proper reinstitution and healing during chronic relapsing inflammatory processes. The activated myofibroblast is the final effector cell that overproduces ECM under the influence of various mediators generated by an intense interplay of classic and non-classic immune cells. Activation and proliferation of myofibroblasts by inflammatory and profibrotic mediators is a central event in the process of normal wound healing and post-operative fibrosis after acute injury. We will mainly discuss our research work on the intestinal myofibroblasts phenotype in gut inflammation and fibrosis and on how proinflammatory mediators from various sources produced in different stages of intestinal inflammation can form profibrotic pathways that eventually lead to tissue scarring through sustained activation of myofibroblasts.

Speaker profile: George Kolios, MD PhD, is a Professor of Pharmacology at the School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.

First degree in Medicine (1980), Specialization in Gastroenterology (1990) and PhD in Gastroenterology (1992), School of Medicine at the University of Athens, Greece. PhD in Pharmacology, Department of Pharmacy and Pharmacology at the University of Bath, U.K., under the supervision of Professor John Westwick (1998). Registrar in Gastroenterology at the Royal United Hospital, Bath, U.K. (1990-1991) and Senior Registrar in the Gastroenterology Department at the Hippokration General Hospital, Athens, Greece (1991-1997). Senior Research Fellow in the Department of Pharmacy and Pharmacology at the University of Bath, U.K. and Honorary Consultant Gastroenterologist at the Royal United Hospital, Bath U.K. (1998 - 2001). Assistant Professor of Gastroenterology at the School of Medicine, University of Crete, Greece (2001-2008) and Professor of Pharmacology at the School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece (2008 - till today). Head of the Laboratories of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Democritus University of Thrace (2008 –2017). Vice-President of the Faculty of Medicine, Democritus University of Thrace (2013 –2017). Director of the Master's Degree Program "Clinical Pharmacology and Therapeutics" at the School of Medicine, Democritus University of Thrace, Greece (2011 - 2018). Member of the Scientific Board of Approvals of the Greek National Organization for Medicines (2008 – 2013). Visiting Professor in Pharmacology, Department of Pharmacy and Pharmacology, University of Bath, U.K. (2001-2013). Visiting Scientist (one year Sabbatical), Laboratory of Molecular Immunology, Mucosal Immunobiology Section, National Institute of Health (NIH), Bethesda, Maryland, U.S.A. (2007).

His work is focused on the field of immunopharmacology, mucosal immunology and fibrosis, mainly on the intestinal inflammation and Inflammatory Bowel Diseases, demonstrating that the mucosal epithelium could be a rich source of various inflammatory mediators, including cytokines, chemokines and nitric oxide, that are involved in inflammation and fibrosis, and could be modified by cytokines derived by T-cell populations. In addition, his work has been focused on the biology and the role of gut subepithelial myofibroblasts in post-inflammatory fibrosis and on the development of in vitro models for the study of gut microbiota, and stromal and immune cells interactions, such as cell cultures and intestinal organoids.