McMurray, Rebecca Jane
Nanoscale surfaces for the long-term maintenance of mesenchymal stem cell phenotype and multipotency.
PhD thesis, University of Glasgow.
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The discovery of stem cells has led to rapid advances in the field of regenerative medicine. Their unique properties, including the ability to self-renew and differentiate make them ideal for the repair/replacement of tissues that have been damaged as a result of disease or injury. Mesenchymal stem cells in particular represent a highly valuable pool of adult stem cells for such regenerative applications due to their accessibility, and potential as an autologous patient derived autologous nature
However current methods for the in vitro expansion of high quality autologous mesenchymal stem cells results in spontaneous differentiation of the stem cell population and a loss of differentiation capacity over time. In vivo, it is the stem cell niche that provides stem cells with the appropriate cues required to maintain stem cell self-renewal. It is proposed that by mimicking these cues using biomaterials, that the self-renewal of mesenchymal stem cells can be controlled in vitro. In this study, a novel nanopit topography was investigated for its effects on the maintenance and growth of mesenchymal stem cells in vitro.
To investigate this, three main aspects of mesenchymal stem cell state were examined in response to this novel nanotopography: maintenance of the stem cell phenotype over time including expression of stem cell markers and differentiation potential over time, changes in signalling pathways associated with differentiation and lastly, the metabolic profile of stem cells.
As a result of this study we have identified a novel nanopit topography, which in the absence of chemical supplements, provides a substrate that is conducive to the maintenance of mesenchymal stem cells. Small RNAs have also been implicated in the regulation of signalling pathways and the metabolic state of stem cells. Furthermore, the ability to produce nanotopographically-patterned substrates using current standard techniques provides an inexpensive, high throughput method for the production of novel tissue culture plastics suitable for the maintenance of mesenchymal stem cells.
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