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Less revascularization of human islets when experimentally transplanted into the liver than at the renal subcapsular site
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-96670OAI: oai:DiVA.org:uu-96670DiVA: diva2:171320
Available from: 2008-02-01 Created: 2008-02-01 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Implantation-Site Dependent Differences in Engraftment and Function of Transplanted Pancreatic Islets
Open this publication in new window or tab >>Implantation-Site Dependent Differences in Engraftment and Function of Transplanted Pancreatic Islets
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Transplanting pancreatic islets into the liver through the portal vein is currently the most common procedure in clinical islet transplantations for treating patients with brittle type 1 diabetes. However, most islet grafts fail within a 5-year period necessitating retransplantation. The vascular connections are disrupted at islet isolation and implanted islets depend on diffusion of oxygen and nutrients in the immediate posttransplantation period. Rapid and efficient revascularization is of utmost importance for the survival and long-term function of transplanted islets.

In this thesis, the influence of the implantation microenvironment for islet engraftment and function was studied. Islets were transplanted into the liver, the renal subcapsular site or the pancreas. Islets implanted into the liver contained fewer glucagon-positive cells than islets implanted to the kidney and endogenous islets. Intraportally transplanted islets responded with insulin and glucagon release to secretagogues, but only when stimulated through the hepatic artery. Thus, the intrahepatic grafts were selectively revascularized from the hepatic artery. The vascular density in human islets transplanted into the liver of athymic mice was markedly lower when compared to human islets grafted to the kidney. Islets implanted into their physiological environment, the pancreas, were markedly better revascularized. Insulin content, glucose-stimulated insulin release, (pro)insulin biosynthesis and glucose oxidation rate were markedly decreased in transplanted islets retrieved from the liver, both when compared to endogenous and transplanted islets retrieved from the pancreas. Only minor changes in metabolic functions were observed in islets implanted into the pancreas when compared to endogenous islets.

The present findings demonstrate that the microenvironment has a major impact on the engraftment of transplanted islets. Elucidating the beneficial factors that promote engraftment would improve the survival and long-term function of transplanted islets. Ultimately, islet transplantation may be provided to an increased number of patients with type 1 diabetes.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 45 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 304
Cell biology, Type 1 diabetes, pancreatic islets, human islets, islet transplantation, vascular engraftment, revascularization, implantation-site, microenvironment, vascular density, insulin release, (pro)insulin biosynthesis, glucose oxidation, Cellbiologi
urn:nbn:se:uu:diva-8418 (URN)978-91-554-7073-9 (ISBN)
Public defence
2008-02-22, B22, BMC, Husargatan 3, Uppsala, 13:15
Available from: 2008-02-01 Created: 2008-02-01Bibliographically approved

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