An assessment of mesenchymal stromal cell function from patients with neck of femur fractures and the development of a three-dimensional culture model

Silverwood, Robert Keith (2020) An assessment of mesenchymal stromal cell function from patients with neck of femur fractures and the development of a three-dimensional culture model. PhD thesis, University of Glasgow.

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Abstract

Osteoporosis represents an ever increasing burden to health care services worldwide. Within the UK alone, over 500 000 fragility fractures secondary to osteoporosis occur each year, resulting in significant morbidity and mortality. Furthermore, the management of these injuries cost health care services billions of pounds. A revolution in the diagnosis and treatment of the disease is required to prevent significant suffering of future generations.

MicroRNAs are known to regulate many key physiological processes, including mesenchymal stromal cell (MSC) differentiation. They have been demonstrated to be abnormally expressed in many musculoskeletal conditions, including osteoporosis. Patients who have suffered a neck of femur fracture are known to be at risk of, or have undiagnosed, osteoporosis. Dysregulated microRNAs have been identified in bone and serum samples of patients with this injury type. Great hope has been placed on the development of targeted therapies to manipulate microRNA expression and improve bone quality.

This study has focussed on rigorously assessing the functionality of MSCs from patients who have suffered a neck of femur fracture. Extracellular MSC markers and differentiation capacity were shown to be significantly altered within this patient group. MicroRNA expression was analysed, and key microRNAs, microRNA-143 and microRNA-31, were manipulated using functionalised gold nanoparticles to further understand their role in MSC differentiation. Furthermore, the metabolomic effect of inhibiting microRNA-31 was explored to further understand its role in osteogenesis. To reduce the gap between in vitro and clinical research an optimal 3D, scaffold free, culture model was identified for bone marrow derived MSCs.

These results provide further insight to the impaired MSC function of patients who have suffered a fragility fracture. Furthermore, the potential of microRNAs to be utilised as a biomarker or therapeutic target for osteoporosis has been reinforced.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: osteoporosis, microRNA, fragility fractures, three-dimensional culture.
Subjects: Q Science > Q Science (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology > Molecular Cell and Systems Biology
Funder's Name: Royal College of Surgeons of Edinburgh (RCSED), Royal College of Surgeons of Edinburgh (RCSED)
Supervisor's Name: Dalby, Professor Matthew J. and Berry, Dr. Catherine C. and Meek, Professor R.M. Dominic
Date of Award: 2020
Depositing User: Mr Robert Keith Silverwood
Unique ID: glathesis:2020-81602
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 21 Aug 2020 09:38
Last Modified: 21 Aug 2020 10:02
URI: http://theses.gla.ac.uk/id/eprint/81602

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