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Mifsud, CAJ, 2025. Development of in-vitro models of the bone marrow stem cell niche. PhD, Nottingham Trent University.
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Abstract
The bone marrow stem cell niche is a complex microenvironment with osteogenic and haematopoietic lineage cells, generated from differentiation of haematopoietic and mesenchymal stem cells (MSCs). A niche is defined by its cells, microenvironment, physical and chemical interactions. The niche is not fully understood with respect to the cellular components, location, and internal interactions. In this study, to develop the understanding of the biological structure and systems underpinning the niche, models were developed focusing on the osteogenic lineage. There is the potential for this work to inform the development of therapeutics, supporting the development of therapeutics in the future.
A fully realised, novel model was developed at the macroscopic level, integrating MSCs and human osteosarcoma (HOS) cells in co-culture, seeded onto a scaffold of decellularised rat bone with mechanical stimulation and cultured in osteogenic media. A model at the microscopic level was then developed utilising cellular control in a manner and extent not previously developed. This was accomplished utilising micro-manipulation techniques using holographic optical tweezers (HOTs) based micromanipulation technique, bespoke equipment that can manipulate cells and other objects in 3D space, allowing the precise positioning of MSCs and HOS on a fragment of decellularised rat bone.
In the macroscopic model, cells, extracellular matrix, and physical and chemical stimuli were incorporated, and a highly significant increase in osteogenic content was detected in comparison with controls. This novel model could be used to understand the complex interactions within the niche better and can be used in drug testing. For the microscopic model, a dynamic patterning system to reproduce two cell types independently and reproducibly in the same dish was developed, allowing MSC and HOS to be patterned together. The use of HOTs in this model allows novel insights into the biological microenvironment of the niche and has great potential to help determine cellular microenvironment function in a wide variety of tissue types.
| Item Type: | Thesis |
|---|---|
| Creators: | Mifsud, C.A.J. |
| Contributors: | Name Role NTU ID ORCID De Girolamo, L. Thesis supervisor LIF3DEGIRLA UNSPECIFIED |
| Date: | May 2025 |
| Rights: | The copyright in this work is held by the author. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed to the author. |
| Divisions: | Schools > School of Science and Technology |
| Record created by: | Jeremy Silvester |
| Date Added: | 27 Jun 2025 15:43 |
| Last Modified: | 27 Jun 2025 15:43 |
| URI: | https://irep.ntu.ac.uk/id/eprint/53843 |
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