Anatomy and Neuroscience - Theses
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ItemOptimizing Stem Cell Models of the Human Gut-immune Barriers( 2024-01)Summary The adult human gut has an area of about 200 to 400 square meters. This massive surface is covered by a layer of epithelial cells that creates a physical barrier to the environment, whilst absorbing nutrients from food. Appropriate regulation of host immune responses to luminal contents helps maintain both tissue and microbial homeostasis in the gut tract. Impaired inflammatory regulation of the immune-epithelial interface is associated with chronic diseases such as inflammatory bowel disease (IBD). Together with the gut epithelium, intestinal macrophages produce immune regulators that control recruitment and activation of adaptive immune processes, including regulatory T cells in the intestine. We know that macrophages are recruited to the developing gut from the earliest stages of organogenesis, however, the role of these cells in healthy gut development has not been widely studied. Most of our knowledge about gut macrophages comes from studying animal models, especially rodents. This project forms part of a larger program of research aimed at understanding the role of macrophages at epithelial barriers associated with skin, gut, and mucosal surfaces. We will use induced pluripotent stem cells to derive macrophages and test optimal co-culture conditions that mimic the immune-epithelial niche. We hypothesize that introduction of macrophages to a gut epithelial model will improve the development and integrity of the in vitro gut epithelium. The hypothesis will be tested using established models of gut epithelium and introducing iPSC-macrophages to assess epithelial barrier integrity, inflammatory reactivity to injury, and immune tolerance of commensal gut bacteria.