Cell Based Therapy for Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD) is a common and costly cause of chronic morbidity in the developed world, which currently affects 85,000 Australians and millions world-wide. IBD comprises two conditions characterised by chronic, idiopathic inflammation of the intestine: ulcerative colitis (UC) and Crohn’s disease (CD), both of which result in considerable morbidity, reduced quality of life and significant occupational loss. The aetiology of the disease is currently unknown, but it is thought to be contributed by a dysregulated immune response. hAEC are non-mesenchymal stem cell (MSC), non-embryonic stem-like cells with similar therapeutic properties to MSC. hAEC display a high degree of plasticity, pluripotency and differentiation, low immunogenicity, immunomodulatory and anti-fibrotic properties. While hAEC therapy has been most significantly studied in neonatal lung disease, it also has significant therapeutic potential in IBD. Exosomes are nanometre-sized extracellular vesicles (40-120 nm) containing cargo consisting of proteins, mRNAs, miRNAs and DNA that are released by parental hAEC as a method of intercellular communication (hAEC Exo). Exosome-based therapeutics are based on the premise that exosomes shed by stem cells exert similar therapeutic effects to whole cells, and they have been shown to exert their effects on neutrophils, macrophages and T cells. Exosome-based therapy is extremely promising from multiple aspects including safety, production and accessibility. This project will investigate how immune cells, stem cells and their derivatives modulate the inflammatory immune response in IBD with the aim to develop them as a therapeutic strategy for inflammatory bowel disease.