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Oral progenitor cells as cell-based treatment for neural damage

Howard-Jones, Rachel Anne 2013. Oral progenitor cells as cell-based treatment for neural damage. PhD Thesis, Cardiff University.
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Abstract

Over the past few decades stem cells have been extensively investigated due to their potentially invaluable therapeutic use. Embryonic stem cells (ESCs) have wide-ranging therapeutic applications in tissue repair and regeneration due to their pluripotent properties and their ability to self-renew indefinitely. However, ethical concerns surround their use and hence alternatives are sought. Adult stem cells (ASCs) have been isolated from various adult tissues including the oral mucosa lamina propria (OMLP). This study aims to isolate ASCs from the OMLP, reprogram these cells to induced pluripotent stem cells (iPSCs) and determine the potential for both to differentiate into functional neurons due to the limited regeneration of neurons in the central nervous system. Such investigations into strategies for the treatment of neural damage are invaluable and timely due to current limitations in the availability of human-derived cells for potential autologous or allogeneic tissue repair. OMLP-PCs represent an ideal cell source for use in regenerative medicine given their ease of isolation, proliferative potential, multipotent properties and immunosuppressive activities. Work in this Thesis has now demonstrated that these oral progenitors expressed numerous pluripotency markers and for the first time, that they could be reprogrammed to iPSCs utilising safer, non-integrating plasmids, thus increasing their potential for use in clinical applications. OMLP-iPSCs were positive for a number of pluripotent stem cell markers including SSEA-4, SSEA-5, TRA-1-60, TRA-1-81, Oct-4 and Sox-2. Moreover, their expression of early stage germ layer markers indicated their potential to differentiate into cell types of the mesoderm, endoderm and ectoderm. OMLP-PCs were also demonstrated within this Thesis to differentiate down an early neural lineage as evidenced by the presence of typical neural markers (Nestin, βIII tubulin, MAP-2 and NF-M). The presence of both ligand-gated and voltage-sensitive calcium channels indicated some limited potential functional phenotype. Unfortunately, utilising the same neural differentiation methodology, OMLP-iPSCs were not able to be similarly driven down a neural pathway. None-the-less this data suggests that OMLP-PCs and OMLP-iPSCs may hold great promise for a wide range of regenerative medicine applications

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Dentistry
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history > QH426 Genetics
R Medicine > RK Dentistry
Funders: Cardiff University School of Dentistry
Date of First Compliant Deposit: 30 March 2016
Last Modified: 30 Jun 2017 03:16
URI: http://orca.cf.ac.uk/id/eprint/52753

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