Development of a biomicrofluidic model of the gastrointestinal-lymphatic interface
Author(s)
Samuel, Jake
Type
Thesis
Abstract
The lymphatics have typically been viewed as the secondary circulatory system of the body with their primary function being to drain fluid, proteins and cellular debris, collectively termed lymph, from the interstitial space. However, it has been recognised that the lymphatics fulfil a wider range of homeostatic processes, and that dysregulation of these processes can result in a variety of diseases. The lymphatics associated with the gut are particularly important as they undertake a number of specialised roles including the absorption of lipids via the chylomicron pathway - an innate lipid transport mechanism where dietary lipids are packaged and secreted by the enterocytes of the gut, taken up by the initial lymphatics and delivered to the peripheral tissues. Interestingly, the intestinal lymphatics have emerged as an interesting site of oral drug delivery as therapeutics can be targeted to the lymphatics by integrating with chylomicron handling processes to increase bioavailability and better treat lymph-mediated disease. Current models of the gut-lymphatic interface are based on animal models and conventional cell culture platforms that do not fully ecapitulate in vivo morphology and function, and therefore, lack predictive power for basic research and the preclinical evaluation of drug candidates. This thesis aims to produce a novel biomicrofluidic model of the gut-lymphatic interface to study these tissues in both health and disease states and
provide a platform to test the lymphotropic capacity of molecules. This work optimises
and characterises the model in the context of in vivo morphology and function,
demonstrates its utility in probing lipid metabolism and shows it can be a valuable tool
to study disease.
provide a platform to test the lymphotropic capacity of molecules. This work optimises
and characterises the model in the context of in vivo morphology and function,
demonstrates its utility in probing lipid metabolism and shows it can be a valuable tool
to study disease.
Version
Open Access
Date Issued
2025-03-01
Date Awarded
01/05/2025
License URL
Advisor
Ces, Oscar
Kamaly, Nazila
Sponsor
Engineering and Physical Sciences Research Council
Publisher Department
Department of Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)