Enhanced bone repair using embryonic stem cells in a mouse model of impaired fracture healing

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dc.contributor.advisorMatyas, John R.
dc.contributor.advisorRancourt, Derrick
dc.contributor.authorTaiani, Jaymi Tiffany
dc.date.accessioned2017-12-18T22:32:34Z
dc.date.available2017-12-18T22:32:34Z
dc.date.issued2012
dc.descriptionBibliography: p. 173-183en
dc.descriptionSome pages are in colour.en
dc.descriptionIncludes copy of ethics approval and copyright permission. Original copies with original Partial Copyright Licence.en
dc.description.abstractFractures that occur in osteoporotic bone typically demonstrate impaired healing or non-union of the bony ends and current treatment methods for these types of injuries are inadequate. The field of tissue engineering offers promising treatment alternatives for diseases and injuries that affect tissues with a limited capacity for repair. Embryonic stem (ES) cells offer advantages over other stem cells types in that these cells are pluripotent, possessing the ability to generate any cell type in the body, and have a high capacity for self-renewal. This thesis describes the development of a novel product for the augmentation of bone fracture repair. Using protocols previously developed by our group, we initially attempted to differentiate bioreactor-expanded ES cells into osteoblasts and chondrocytes in stirred suspension culture systems. Surprisingly, we found that the bioreactor culture environment promoted ES cell pluripotency, resulting in limited cell differentiation. Through further experimentation, we found that exposure to a collagen I extracellular matrix induced osteoblastic differentiation of ES cells with greater efficacy than medium supplementation. Furthern1ore, the cell-loaded collagen constructs formed mineralized tissue nodules following subcutaneous implantation into immune-compromised mice. Subsequently, we developed a fracture model, using both nonnal and osteoporotic mice, to test the efficacy of the constructs to contribute to bone repair at an orthotopic site in vivo. Bone formation was enhanced in the mice treated with cell-loaded collagen constructs and the implanted cells were identified at the fracture site for up to 8 weeks. The formation of a small ectopic soft tissue mass in some of the recipient mice suggests that the collagen I matrix reduced but did not eliminate the tumorigenic potential of the cells. To our knowledge, the studies presented herein are the first of their kind to demonstrate the efficacy of a stem cell therapy for fracture repair in osteoporotic bone in vivo. The findings presented in this thesis highlight the importance of using an orthotopic implantation system to test in vivo functionality of ES cell-derived cells and provide an important foundation for future studies looking to develop stem cell therapies for bone injuries in larger animal models and people.
dc.format.extentx, 186 leaves : ill. ; 30 cm.en
dc.identifier.citationTaiani, J. T. (2012). Enhanced bone repair using embryonic stem cells in a mouse model of impaired fracture healing (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/4815en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/4815
dc.identifier.urihttp://hdl.handle.net/1880/105816
dc.language.isoeng
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.titleEnhanced bone repair using embryonic stem cells in a mouse model of impaired fracture healing
dc.typedoctoral thesis
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
ucalgary.thesis.accessionTheses Collection 58.002:Box 2096 627942968
ucalgary.thesis.notesUARCen
ucalgary.thesis.uarcreleaseyen
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