Enhancing osteoporotic fracture healing with p21-/- induced pluripotent stem cells

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dc.contributor.advisorKrawetz, Roman, J
dc.contributor.authorOlsen, Alexandra B
dc.contributor.committeememberRancourt, Derrick
dc.contributor.committeememberDuncan, Neil, A
dc.dateFall Convocation
dc.date.accessioned2023-05-11T04:26:54Z
dc.date.embargolift2023-08-25
dc.date.issued2021-08-25
dc.description.abstractFollowing a fracture, bone regeneration is dependent on the recruitment of mesenchymal progenitor cells (MPCs). After recruitment of MPCs, regeneration will proceed by one of the two primary osteogenic pathways; intramembranous ossification or endochondral ossification, with the latter being the most common fracture healing pathway. Diseases that disrupt bone homeostasis such as osteoporosis result in prolonged endochondral ossification and as a result, osteoporotic fracture healing results in suboptimal bone regeneration(1). Thus, it is of the utmost importance to determine ways to enhance osteoporotic fracture healing. Of potential interest is the tumour suppressor p21-/- as it has been reported that p21-/- induced pluripotent stem cells (iPSCs) have increased bone and cartilage differentiation potential(2). Our lab has reported that osteoporotic p21-/- mice have decreased trabecular bone loss and also shown that p21-/- mice have increased bone regeneration following a tibia burr hole injury, a model that promotes intramembranous ossification(3). However, the burr hole model is not clinically relevant as it does not mimic commonly occurring fractures. Therefore, the purpose of this thesis was two-fold: first, to assess the regenerative potential of p21-/- mice following a fracture that promotes endochondral ossification and second, to determine the potential therapeutic effects of transplanting p21-/- (iPSCs) into an osteoporotic fracture. It was observed that p21-/- mice demonstrated increased bone regeneration post-fracture under normal or osteoporotic conditions. When p21-/- or C57BL/6 iPSCs were transplanted into the fracture site of an osteoporotic mouse, increased bone regeneration was observed. Furthermore, engraftment of these exogenous iPSCs into the fracture callus was observed. Interestingly, only the transplantation of p21-/- iPSCs resulted in bone that was tougher 4 weeks post-fracture. Taken together, these results suggest that treatment with exogenous iPSCs is a promising option to enhance bone regeneration under osteoporotic conditions. Further elucidating the contributions of iPSCs to bone regeneration is required prior to translating this fundamental knowledge into a clinical setting. Of critical importance, we need to understand the mechanisms by which iPSCs contribute to bone regeneration and determine how best to handle these cells to maximize healing potential and minimize tumorgenicity post-transplant.
dc.identifier.citationOlsen, A. B. (2021). Enhancing osteoporotic fracture healing with p21-/- induced pluripotent stem cells (Master thesis). University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca .
dc.identifier.urihttp://hdl.handle.net/1880/116305
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/dspace/41149
dc.language.isoEnglish
dc.publisher.facultySchulich School of Engineering
dc.subject.classificationEngineering--Biomedical
dc.titleEnhancing osteoporotic fracture healing with p21-/- induced pluripotent stem cells
dc.typemaster thesis
thesis.degree.disciplineEngineering – Biomedical
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
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