Enzyme-responsive RGD-functionalised substrates to influence mesenchymal stem cells

Roberts, Jemma Natasha (2013) Enzyme-responsive RGD-functionalised substrates to influence mesenchymal stem cells. PhD thesis, University of Glasgow.

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Abstract

Regenerative medicine is a rapidly expanding field of science with an exhaustive volume of literature published on the different strategies used to repair diseased or injured tissue. Recently, stem cells have emerged as a promising candidate in this regard owing to their involvement in embryogenesis, homeostatic turnover and normal tissue repair. Despite this potential, stem cell-based therapies have yet to be fully established in a clinical setting owing to complications associated with their limited numbers, immunogenicity, tumour formation and the ethical considerations surrounding their usage. Furthermore, the mechanisms underlying stem cell differentiation are complex and not fully understood, thus expanding stem cell numbers and predictably directing their commitment toward a desired lineage, represent a major challenge for tissue regeneration strategies. In an attempt to circumvent these problems there is currently a rising interest in biomimetic materials that aim to reproduce the physical architecture, chemical composition and plasticity of the in vivo extracellular environment in an in vitro setting. Furthermore, the need to expand stem cells while maintaining the stem cell phenotype has prompted many to look to the stem cell niche for answers. At the centre of most cellular responses to the physical cues embedded within the ECM are integrins. Integrins are mechanosensitive membrane spanning receptors that link the ECM to the cytoskeleton and thus transmit information from outside the cell into the nucleus, affecting gene transcription via a series of intracellular signalling cascades. To that end, many biomimetic systems incorporate integrin- binding ligands such as the tripeptide RGD. In this work glass surfaces functionalised with RGD were used to study changes in mesenchymal stem cell (MSC) responses to increased integrin binding by using an enzymatic ‘switch’ to reveal surface-bound RGD peptides that have been masked by a large chemical cap (Fmoc). The results of this work demonstrated that RGD- functionalised substrates can support MSC growth and influence them to commit to a particular fate. MSCs on surfaces where integrin-ligand binding was blocked developed a fibroblast-like phenotype whereas MSC grown on surfaces that were later enzymatically digested to reveal the underlying RGD ligands developed an osteoblast phenotype similar to RGD controls.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > Q Science (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Funder's Name: UNSPECIFIED
Supervisor's Name: Dalby, Dr. Matthew and Ulijn, Prof. Rein
Date of Award: 2013
Depositing User: Miss Jemma Natasha Roberts
Unique ID: glathesis:2013-4816
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 22 Jan 2014 12:37
Last Modified: 22 Jan 2014 12:37
URI: http://theses.gla.ac.uk/id/eprint/4816

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