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dc.contributor.advisorLally, Caitriona
dc.contributor.authorMATHIEU, PATTIE SMITH
dc.date.accessioned2020-04-16T08:11:19Z
dc.date.available2020-04-16T08:11:19Z
dc.date.issued2020en
dc.date.submitted2020
dc.identifier.citationMATHIEU, PATTIE SMITH, Multipotent vascular stem cells and the effects of cyclic tensile strain, collagen structure and stenting on medial vascular cell populations, Trinity College Dublin.School of Engineering, 2020en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/92298
dc.descriptionAPPROVEDen
dc.description.abstractAtherosclerosis is one of the leading causes of mortality worldwide, and presents as a narrowing or occlusion of an artery. Interventions to re-open the arterial lumen can result in re-occlusion through intimal hyperplasia. Historically only de-differentiated vascular smooth muscle cells were thought to contribute to intimal hyperplasia. However recent evidence suggests that resident medial multipotent vascular stem cells (MVSC) may also play a role. Therefore the strain response of MVSCs was investigated since these resident cells are also subjected to strain within their native environment. First, the differences between MVSC and vascular smooth muscle cell (VSMC) strain response were investigated by applying 1 Hz cyclic equiaxial strain for 24 hours, with or without TGF-β1, and evaluating the phenotypic response. In order to investigate a strain environment more similar to the one experienced in vivo, uniaxial 1Hz cyclic uniaxial tensile strain was applied at three amplitudes around a mean strain of 5%, (4-6%, 2-8% and 0-10%) for 24 or 72 hours to both cell types. The effect of extracellular matrix (ECM) was assessed by applying 0-10% 1Hz uniaxial tensile strain for 10 days. Finally, MVSC seeded on decellularized porcine carotid arteries were indented with a single wire strut either statically or dynamically to investigate MVSC response to stenting. Cells were evaluated for alignment and proliferation. In equiaxial strain experiments MVSC became more contractile when exposed to strain, while VSMC showed no phenotypic change. Under uniaxial tensile strain, both cell types exhibit strain avoidance after 24 hours. The strain avoidant response was greater for MVSC, at 24 hours while VSMC strain avoid to a greater degree after 72 hours. Both cell types also increase strain avoidance as strain amplitude is increased. MVSC and VSMC show distinct differences when strained on native ECM. Both MVSC and VSMC align parallel to the collagen fibre direction when left unstrained. When strained parallel to fibre direction, MVSC remained aligned with fibre direction, while in some cases VSMC showed strain avoidant realignment. MVSC aligned in the direction of strain showed increased proliferation, but VSMC aligned with strain showed a decreased cell number. When MVSC were tested with simulated stent strut indentation, they developed patches of dense, highly proliferative cells, mimicking what is seen in in-stent restenosis. These experiments demonstrate for the first time how the mechano-sensitivity of MVSC may play a role in in-stent restenosis. This further emphasizes the importance of strain and ECM structure in controlling the response of vascular cells in tissue engineering applications.en
dc.language.isoenen
dc.publisherTrinity College Dublin. School of Engineering. Discipline of Mechanical & Manuf. Engen
dc.rightsYen
dc.subjectMultipotent Vascular Stem Cellsen
dc.subjectVascular Smooth Muscle Cellsen
dc.subjectTensile Strainen
dc.subjectExtracellular Matrixen
dc.subjectIn-Stent Restenosisen
dc.titleMultipotent vascular stem cells and the effects of cyclic tensile strain, collagen structure and stenting on medial vascular cell populationsen
dc.typeThesisen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionthesis_dissertationsen
dc.type.supercollectionrefereed_publicationsen
dc.type.qualificationlevelDoctoralen
dc.identifier.peoplefinderurlhttps://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:MATHIEUPen
dc.identifier.rssinternalid215710en
dc.rights.ecaccessrightsopenAccess


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