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Title: Automation of human umbilical cord-derived mesenchymal stem cell culture for clinical applications
Author: Ramasamy, Gayatri
ISNI:       0000 0004 7970 7331
Awarding Body: Loughborough University
Current Institution: Loughborough University
Date of Award: 2019
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Mesenchymal stem cells (MSCs) are more desirable than embryonic stem cells (ESCs) for clinical applications, mostly due to reduced ethical concerns, ease in expansion, cellular plasticity, and reduced potential for tumorigenesis. They have the capability to replicate as undifferentiated cells or to differentiate into bone, cartilage, fat, muscle, tendon and marrow stromal therefore, they hold great potential for cell therapies. However, for MSCs to be successfully commercialised, well-defined, reproducible and scalable manufacturing processes need to be developed since the transition of these studies from the laboratory to industrial scale processes with consistent outputs is a major challenge. Since the cells themselves may be the final product so the quality of the manufactured cells needs to be ensured throughout the entire bioprocess. In this doctorate, the development of a robust MSCs expansion process using an automated platform was investigated. Since it was identified that there was a lack of in-depth knowledge of the automated MSC culture process, the study focused on in-depth characterisation of the automated system and also on the automated expansion methods. These findings were used to aid the development of a novel robust automated MSC expansion process. The manual expansion process was used as the baseline process. This study used model cell lines for the intial characterisation and process development work to ensure the aim and the objectives can be achieved in a cost effective manner. However, the developed work was later tested and enhanced using MSCs. In order to demonstrate clinical relevance, the developed process was tested with early passage MSCs and analyses were performed on the cells produced to illustrate that they were capable of meeting the requirements set by the International Society of Cellular Therapy (ISCT). The results obtained with the final MSC expansion work demonstrated that there was no significant difference in terms of yield between the automated and the manual process (p > 0.05) and the yields obtained compared well with those reported in literature for the static manual cell culture processes. Most importantly, cells from both processes were able to retain their immunophenotype, multipotency and ability to attach to tissue culture plastic. This study also demonstrated that Stem Pro xeno-free medium can support the growth and expansion of MSCs.
Supervisor: Not available Sponsor: Loughborough University
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Chemical Engineering not elsewhere classified