Microscale Tissue Engineering and Contributors of the Cellular Niche

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dc.contributor.advisorUngrin, Mark D.
dc.contributor.authorAl-Ani, Abdullah
dc.contributor.committeememberBiernaskie, Jeff A.
dc.contributor.committeememberKallos, Michael S.
dc.contributor.committeememberRancourt, Derrick E.
dc.contributor.committeememberHirota, Simon Andrew
dc.contributor.committeememberGratzer, Paul F.
dc.date2019-11
dc.date.accessioned2019-06-03T20:34:37Z
dc.date.available2019-06-03T20:34:37Z
dc.date.issued2019-05-31
dc.description.abstractThe behaviour of cells is modulated by their microenvironment or ‘niche’. While cellular therapies offer promising curative solutions for many diseases, the efficacy of transplanted cells is often hampered by a suboptimal microenvironment. One strategy to overcome this limitation is to reconstruct the niche of the cells of interest prior to transplantation. The central aim of this thesis is to develop novel tissue engineering approaches to further understand and reconstitute the cellular niche. While these approaches were specifically validated in the retinal and islet systems, they were also designed to be easily implemented in other biological systems. One project showcases a novel scaffold-free, scalable and injectable retinal pigment epithelium (RPE) microtissue for minimally-invasive transplantation. While RPE transplantation holds great potential to cure various retinal degenerative diseases, cells transplanted as cellular suspension exhibit suboptimal survival and function. Conversely, transplanting RPE as coherent cellular sheets has yielded better outcomes, but they are complex to transplant and produce at large scale. Our RPE microtissues were designed to capture the benefit of both approaches: namely, simplicity of production and transplantation, as well as enhanced performance. We found that our RPE microtissue exhibited superior cellular behaviour in terms of gene expression and in vitro function when compared to standard adherent culture. Another project presents a unique approach to produce transplants with a reconstituted cellular niche. This approach aims to repopulate the niche by incorporating finite amounts and proportions of niche cells into transplantable constructs. Using it enabled us to produce size-controlled pseudoislet constructs that contained various proportions of mesenchymal stem cells (MSCs), fibroblast and endothelial cells, and to quantitatively evaluate their in vitro performance. Further, applying this approach led us to discover more than one favourable condition that yielded improvements in islet cell performance in vitro. While the islets of Langerhans were used for biological validation, the approach was designed to be broadly applicable to various biological systems. In sum, this thesis offers several novel approaches for scientists to better understand and enhance the cellular niche. The simplicity, accessibility and scalability of these approaches render them suitable for both scientific applications and clinical translation.en_US
dc.identifier.citationAl-Ani, A. (2019). Microscale Tissue Engineering and Contributors of the Cellular Niche (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/36618
dc.identifier.urihttp://hdl.handle.net/1880/110467
dc.language.isoengen_US
dc.publisher.facultySchulich School of Engineeringen_US
dc.publisher.institutionUniversity of Calgaryen
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.en_US
dc.subjectTissue Engineeringen_US
dc.subjectCell replacement therapyen_US
dc.subjectNiche Engineeringen_US
dc.subjectRetinaen_US
dc.subjectIslets of Langerhansen_US
dc.subjectPseudoisletsen_US
dc.subjectRetinal Pigment Epitheliumen_US
dc.subjectOxygenen_US
dc.subject.classificationBiologyen_US
dc.subject.classificationBiology--Cellen_US
dc.subject.classificationEngineeringen_US
dc.titleMicroscale Tissue Engineering and Contributors of the Cellular Nicheen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineEngineering – Biomedicalen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrue
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