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Title: Multifactorial analysis of mesenchymal stem cell properties for storage and transportation
Author: D'Agostino, Fabio Salvatore
ISNI:       0000 0004 6499 6871
Awarding Body: Newcastle University
Current Institution: University of Newcastle upon Tyne
Date of Award: 2017
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Using living cells to treat disease is known as cell therapy and holds the potential to revolutionize healthcare. An increasing number of cell-based products are approaching the late clinical development phase, with human mesenchymal stem cells, which have chondrogenic, osteogenic and adipogenic differentiation capacity, being one of the most widely studied. For these new medicinal products, preserving their therapeutic potential throughout the supply chain is challenging. Current approaches are based on cryopreservation, where cells are cooled to -80 °C or lower, on hypothermic preservation, where cells are cooled to 2-8 °C, and on controlled room temperatures, with cells at 15-25 °C. However, these methods suffer from limitations and alternative approaches are required. The aim of this thesis was to investigate a novel temperature range (26-37 °C) for storage and transportation and, for the first time, to combine temperature with a variable oxygen tension (3-20 %) over a simulated shelf life of 5 or 7 days. Two models were investigated: undifferentiated human bone marrow derived mesenchymal stem cells and cartilage discs derived from these cells. The investigation was based on the use of a statistical design of experiment where temperature, oxygen and storage duration are the input factors while viability, metabolite concentrations and gene expression are the output factors. The results showed that temperature and oxygen modulate metabolic activity and subsequent differentiation potential, with interaction effects between temperature and oxygen being readily identifiable. Predictive models were subsequently developed, with case studies demonstrating how such models can be used as a decision support tool for the design of a transportation device for mesenchymal stem cells and their differentiated products. 3 Overall, this thesis demonstrates the need for a multifactorial approach for the development of a storage and transportation solution of cell-based medicinal products and offers guidance as to how this may be possible.
Supervisor: Not available Sponsor: Engineering and Physical Sciences Research Council (EPSRC) ; Tower Cold Chain
Qualification Name: Thesis (Eng.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available