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Title: Technologies for expansion, transport and delivery of cell therapies for regenerative medicine applications
Author: Gould, Toby William Albert
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2013
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Cell therapy is an emerging facet of the regenerative medicine discipline. Innovation in this field is providing new solutions for the treatment of diseases and lost functionality of the human body. These are therapies that have cells as the active agent and in particular human mesenchymal stem cells (hMSCs) are proven to be useful in this context. For these treatments to be widely available and marketed widely there is a requirement to overcome bottle necks within the product life cycle. One such bottle neck is the reproducible generation of enough cells on a mass manufacturing scale. Following this is the transport of the therapeutic cells from the production facility to the care giving facility without the extra complication of cryopreservation. The final aspect of the life cycle discussed here is the delivery of the cells to the patient. In this case as part of a tissue-engineering construct for the regeneration of mastoid bone. A temperature responsive magnetic particle gel dispersion was demonstrated as a surface capable of supporting the growth of a 3T3 cell line. It was also shown that cells grown on this surface could be subcultured on this surface by reducing the temperature to 10 DC and applying a magnetic field as to separate the cells. These cells were seeded on to new gels and showed that the population increased with time. A model of a system capable of transporting live hMSCs in sealed units was investigated. The multivariate . experiment took into consideration different temperatures of 4 DC, 23 DC, 27 DC and 37 DC, varying cell density of 5 x 104 and 10 x 104 cells per well and media volumes set at 1 ml and 2 ml per well. The results showed that over a 7 day period the most important factor was the time at any given condition . The factors of media volume and cell density had no bearing on the measured outcome of percentage of viable or apoptotic cells as measured by flow cytometry. For the treatment of patients following mastoidectomy a material capable of regenerating the mastoid air cell structure and releasing a broad spectrum antibiotic ciprofloxacin was investigated. The material based on PLGA/PEG micro particles with included alginate gel beads that is pastable at room temperature and sintersat body temperature to form a higly porous scaffold material. It was shown to support the growth of progenitor hMSCs an'd to release antibiotic with varying profiles depending upon the type of formulation . This study highlights the importance for new technologies and methods to propel cell therapies from the laboratory setting through to commercialisation and the marketplace. ii
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available