Activation of the resident Skeletal Stem Cell (SSC) for articular cartilage regeneration.
The aim of this PhD thesis is to validate that a commonly performed surgical therapy used to treat patients with osteoarthritis (OA), microfracture (MF), can activate tissue-resident Skeletal Stem Cells (SSC) from distal femurs. In Chapter 1 we introduce the topics related to the thesis including; OA overview, stem cell therapies and current stem cell trials used for OA. In Chapter 2 we show that with age there is a reduction in the number of SSC in the articular surface of mouse distal femurs. In Chapter 3 we demonstrate that there is an local, transient activation of SSC following acute MF surgical stimulation. In Chapter 4 we show that augmentation of the niche with growth factors bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor receptor 1 (VEGFR1) following injury results in the regeneration of hyaline-like cartilage. In Chapter 5 we translate our mouse findings in vivo utilising our human xenograft model. In our human xenograft model we confirm that following acute injury there is a similar activation in tissue resident SSC. Niche augmentation with BMP2 and VEGFR1 in the human xenograft model leads to de novo human cartilage formation in a bone niche.
First SupervisorProf Sean Carroll
Second SupervisorMr Dara Kavanagh
CommentsA thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2019.
Published CitationMurphy MP. Activation of the resident Skeletal Stem Cell (SSC) for articular cartilage regeneration [PhD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2019
Degree NameDoctor of Philosophy (PhD)
Date of award30/11/2019
- Doctor of Philosophy (PhD)