Modelling an in vitro haematopoietic stem cell niche using poly (ethyl acrylate) surfaces

Sweeten, Paula Emily (2019) Modelling an in vitro haematopoietic stem cell niche using poly (ethyl acrylate) surfaces. PhD thesis, University of Glasgow.

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Haematopoietic stem cells (HSCs) are multipotent stem cells with the capacity to either self-renew or differentiate into oligolineage progenitor cells, and then mature blood cells. HSCs have a diverse range of medical applications, and HSC transplantation can be used to cure certain types of blood cancer including leukaemia and lymphoma. However, current cell culture techniques do not allow for the long-term culture of HSCs, and have restricted the extent to which HSCs numbers can be expanded in the laboratory. Thus, it is necessary to develop culturing techniques that allow for long-term culture and expansion of HSC numbers in the lab.
HSCs reside in the bone marrow alongside a second type of multipotent stem cell termed mesenchymal stem cells (MSCs). Both cell types exist in a unique microenvironment called ‘the niche’, which is responsible for regulating differentiation, proliferation and maintenance of these stem cells. It is understood that MSCs associate with HSCs in the niche, and support maintenance of the HSC phenotype by expressing HSC maintenance factor transcripts. Consequently, developing niche models featuring MSCs has been the focus of recent research aimed at achieving the long-term culture of HSCs.
Many recent studies have focused on incorporating the use of MSCs and soluble growth factors in the media of MSC/HSC co-cultures to promote the long-term culture of HSCs. However, the high concentrations of media growth factors required to elicit responses in HSC long-term repopulating abilities are costly and have been shown to cause off-target effects. Use of substrate-bound growth factors can induce sustained signalling, meaning reduced quantities of growth factors can elicit similar responses in a more-effective way.
This study has focused on the development of a 3D in vitro bone marrow niche system, utilising a range of novel biomaterials including: a substrate composed of poly (ethyl acrylate) (PEA) substrate and fibronectin; a combination of substrate-bound growth factors; a monolayer of MSCs; a type I collagen gel capable of mimicking the elastic properties of the niche and a media capable of supporting an MSC/HSC co-culture. Results show the potential of this system to maintain a greater number of HSCs in their stem cell state, relative to controls.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Mesenchymal stem cells, stem cells, haematopoietic stem cells, HSC niche, bone marrow, niche.
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Funder's Name: Engineering and Physical Sciences Research Council (EPSRC)
Supervisor's Name: Dalby, Professor Matthew, Mountford, Dr. Jo and Salmeron-Sanchez, Professor Manuel
Date of Award: 2019
Depositing User: Miss Paula E. Sweeten
Unique ID: glathesis:2019-41188
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 01 May 2019 14:13
Last Modified: 05 Mar 2020 21:20
Thesis DOI: 10.5525/gla.thesis.41188
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