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Title: Cell and extracellular matrix interactions : a biomimetic approach to use cryptic extracellular information to regulate the epithelial-to-mesenchymal transition
Author: Wang, Alex
ISNI:       0000 0004 8504 3471
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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The extracellular matrix (ECM) provides dynamic biochemical and structural cues that control cell proliferation, signalling, and homeostasis. A critical feature of the ECM is its cryptic sites, hidden biologically active sites exposed through structural alteration or proteolytic cleavage events. In this project, a cryptic signalling fragment derived from the laminin-111 protein is explored as a potential control switch for the epithelial-to- mesenchymal transition (EMT), a critical process in development, wound healing, and cancer progression. One EMT-related pathology in wound healing is fibrosis, the accumulation of excess scar tissue that inhibits normal tissue function. A potential strategy in treating this disease is to control or slow the EMT process during wound healing to prevent epithelial cells from transforming into myofibroblasts that contribute to fibrotic tissue. The effect of the cryptic fragment is characterised in Mus musculus mammary gland epithelial cells (NMuMGs) undergoing transforming growth factor β (TGFβ) induced EMT using imaging, biochemical, and molecular-biological techniques. The fragment is then used to engineer a biomimetic basement membrane (BM), using polydopamine coated poly(ε- caprolactone) as the structural scaffold. This system allows stable binding of proteins, as well as providing a suitable surface for epithelial cell proliferation. In this work it is shown that the cryptic fragment directly down-regulates crucial EMT genes in this artificial BM system in NMuMGs, providing a potential reduction of fibrosis pathology. Future and ongoing work will continue to optimise the system and lead to other applications of EMT control both for in vivo and in vitro studies. This project explores the still widely unused potential of cryptic ECM information in tissue engineering.
Supervisor: Stevens, Molly Sponsor: Imperial College London
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral