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dc.contributor.advisorWilliams, Stuart K.en_US
dc.contributor.authorHiscox, Alton
dc.creatorHiscox, Altonen_US
dc.date.accessioned2011-12-06T14:20:44Z
dc.date.available2011-12-06T14:20:44Z
dc.date.issued2008en_US
dc.identifier.urihttp://hdl.handle.net/10150/196072
dc.description.abstractIslet transplantation for the purpose of treating insulin-dependent diabetes is currently limited by several factors, most significantly, islet survival post transplantation. In the following dissertation, a tissue-engineered prevascularized pancreatic encapsulating device (PPED) was designed, developed, and evaluated. Microvessel fragments placed within a 3-dimensional collagen-based matrix produce and secrete vascular endothelial growth factor, and inosculate with the host circulation. Isolated islets placed within collagen gels exhibited four-fold more insulin release in response to glucose stimulation than islets in tissue culture. The insulin released by β-cells in islets encapsulated in collagen exhibited unobstructed diffusion within the collagen gels. Subsequent studies evaluated the ability to create a sandwich comprised of two layers of prevascularized collagen gels around a central collagen gel containing islets. In vitro characterization of the islets within these constructs showed that islets are functional and respond to glucose stimulation. The PPEDs were implanted subcutaneously into SCID mice. Islet survival was assessed after 7, 14, and 28 days. Immunohistochemical analysis was performed on the implants to detect insulin and the presence of intraislet endothelial cells. At all time points, insulin was localized in association with intact and partially dissociated islets. Moreover, cells that exhibited insulin staining were co-localized with intraislet endothelial cells. Lastly, dextran-perfused PPEDs showed host perfusion throughout the implant, including perfusion to structures that are morphologically consistent with pancreatic islets. These data indicate that the PPED enhances islet survival by supporting islet viability, by maintaining intraislet endothelial cells, and by enhancing reperfusion to the islets.
dc.language.isoENen_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.subjectdiabetesen_US
dc.subjectisletsen_US
dc.subjectprevascularizeden_US
dc.subjectpancreaticen_US
dc.subjectencapsulationen_US
dc.titleDevelopment, Characterization, and Assessment of a Tissue-Engineered Prevascularized Pancreatic Islet Encapsulation Deviceen_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.contributor.chairWilliams, Stuart K.en_US
dc.identifier.oclc659748510en_US
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.leveldoctoralen_US
dc.contributor.committeememberLimesand, Seanen_US
dc.contributor.committeememberHoying, Jamesen_US
dc.contributor.committeememberLynch, Ronen_US
dc.identifier.proquest2577en_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.namePhDen_US
refterms.dateFOA2018-06-05T22:44:19Z
html.description.abstractIslet transplantation for the purpose of treating insulin-dependent diabetes is currently limited by several factors, most significantly, islet survival post transplantation. In the following dissertation, a tissue-engineered prevascularized pancreatic encapsulating device (PPED) was designed, developed, and evaluated. Microvessel fragments placed within a 3-dimensional collagen-based matrix produce and secrete vascular endothelial growth factor, and inosculate with the host circulation. Isolated islets placed within collagen gels exhibited four-fold more insulin release in response to glucose stimulation than islets in tissue culture. The insulin released by β-cells in islets encapsulated in collagen exhibited unobstructed diffusion within the collagen gels. Subsequent studies evaluated the ability to create a sandwich comprised of two layers of prevascularized collagen gels around a central collagen gel containing islets. In vitro characterization of the islets within these constructs showed that islets are functional and respond to glucose stimulation. The PPEDs were implanted subcutaneously into SCID mice. Islet survival was assessed after 7, 14, and 28 days. Immunohistochemical analysis was performed on the implants to detect insulin and the presence of intraislet endothelial cells. At all time points, insulin was localized in association with intact and partially dissociated islets. Moreover, cells that exhibited insulin staining were co-localized with intraislet endothelial cells. Lastly, dextran-perfused PPEDs showed host perfusion throughout the implant, including perfusion to structures that are morphologically consistent with pancreatic islets. These data indicate that the PPED enhances islet survival by supporting islet viability, by maintaining intraislet endothelial cells, and by enhancing reperfusion to the islets.


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