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Photonic discrimination and specific targeting of vascular stem cells.
Molony, Claire
Cardiovascular disease remains the leading cause of death and disability world-wide. The current treatment options include balloon angioplasty and the deployment of drug-eluting stents (DES) coated with anti-mitotic drugs to prevent intimal-medial thickening (IMT). Despite this, an unacceptably high failure rate remains due to non-specific targeting of cells and drug-depletion over time. The source of the cells contributing to IMT remains controversial; one theory suggests a reprogramming of native differentiated vascular smooth muscle cells (SMC) while the other proposes myogenic differentiation of resident vascular and/or circulating stem cells. Resolution of this controversy through identification of the source of the contributing cells would greatly assist in the development of future drug targeting strategies using novel DES platforms. The use of photonics and vibrational spectroscopy is gaining popularity for disease diagnosis. Both platforms have the ability to yield cellular and molecular information about cells and tissues label-free, making them attractive technologies for analysing biological specimen. The first main objective of this work was to analyse individual cells from normal (healthy) and arteriosclerotic (diseased) vessels ex vivo using autofluorescence (AF) in response to broadband light and to compare their AF signatures to undifferentiated stem cells and their myogenic progeny in vitro. The second aim was to use vibrational spectroscopy (Raman and FTIR) to examine undifferentiated stem cells, their myogenic and osteogenic progeny and and further compare their spectra to re- programmed differentiated SMC. Finally, a novel therapeutic platform for targeting stem cell-derived myogenic progeny using magnetic nanoparticles was developed. Using pharmacological inhibitors of glycogen synthase 3 beta (GSK3β), the effects on Notch, a well known mediator of myogenic differentiation were first evaluated in vitro. Further to this, a prototype GSK3β inhibitor was incorporated into a novel drug delivery system consisting of polymer coated Fe304 magnetic nanoparticles which can be systemically administered and specifically targeted to bare-metal stents by an external magnetic field.
Keyword(s): Biotechnology; Microfluidics; Spectrum analysis; Cell biology; Molecular biology; Diseases; Health
Publication Date:
Type: Other
Peer-Reviewed: Unknown
Language(s): English
Contributor(s): Cahill, Paul A.
Institution: Dublin City University
Citation(s): Molony, Claire (2017) Photonic discrimination and specific targeting of vascular stem cells. PhD thesis, Dublin City University.
Publisher(s): Dublin City University. School of Biotechnology
File Format(s): application/pdf
Related Link(s):
First Indexed: 2018-05-15 06:05:33 Last Updated: 2019-02-09 06:11:26