Development, Characterization, and Assessment of a Tissue-Engineered Prevascularized Pancreatic Islet Encapsulation Device

Persistent Link:
http://hdl.handle.net/10150/196072
Title:
Development, Characterization, and Assessment of a Tissue-Engineered Prevascularized Pancreatic Islet Encapsulation Device
Author:
Hiscox, Alton
Issue Date:
2008
Publisher:
The University of Arizona.
Rights:
Copyright © 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.
Abstract:
Islet 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.
Type:
text; Electronic Dissertation
Keywords:
diabetes; islets; prevascularized; pancreatic; encapsulation
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Physiological Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Williams, Stuart K.
Committee Chair:
Williams, Stuart K.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleDevelopment, Characterization, and Assessment of a Tissue-Engineered Prevascularized Pancreatic Islet Encapsulation Deviceen_US
dc.creatorHiscox, Altonen_US
dc.contributor.authorHiscox, Altonen_US
dc.date.issued2008en_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.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.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectdiabetesen_US
dc.subjectisletsen_US
dc.subjectprevascularizeden_US
dc.subjectpancreaticen_US
dc.subjectencapsulationen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorWilliams, Stuart K.en_US
dc.contributor.chairWilliams, Stuart K.en_US
dc.contributor.committeememberLimesand, Seanen_US
dc.contributor.committeememberHoying, Jamesen_US
dc.contributor.committeememberLynch, Ronen_US
dc.identifier.proquest2577en_US
dc.identifier.oclc659748510en_US
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