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Beneficial role of pancreatic microenvironment for angiogenesis in transplanted pancreatic islets
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2009 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 18, no 1, 23-30 p.Article in journal (Refereed) Published
Abstract [en]

Pancreatic islets implanted heterotopically (i.e., into the kidney, spleen, or liver) become poorly revascularized following transplantation. We hypothesized that islets implanted into the pancreas Would become better revascularized. Islets isolated from transgenic mice expressing enhanced yellow fluorescent protein (EYFP) in all somatic cells were Cultured before they were implanted into the pancreas or beneath the renal capsule of athymic mice. Vascular density was evaluated in histological sections 1 month posttransplantation. EYFP was used as reporter for the transgene to identify the transplanted islets. Islet endothelial cells were visualized by staining with the lectin Bandeiraea simplicifolia (BS-1). Capillary   numbers in intrapancreatically implanted islets were only slightly lower than those counted in endogenous islets, whereas islets implanted   beneath the renal capsule had a markedly lower vascular density. In order to determine if this high graft vascular density at the   intrapancreatic site reflected expansion of remnant donor endothelial  cells or increased ingrowth of blood vessels from the host. also islets  from Tie2-green fluorescent protein (GFP) mice (i.e., islets with fluorescent endothelial cells) were transplanted into the pancreas or beneath the renal capsule of athymic mice. These islet grafts revealed that the new vascular structures formed in the islet grafts contained very few GFP-positive cells, and thus mainly were of recipient origin. The reason(s) for the much better ingrowth of blood vessels at the intrapancreatic site merits further studies, because this may help us form strategies to overcome the barrier for ingrowth of host vessels also into islets in heterotopic implantation sites.

Place, publisher, year, edition, pages
2009. Vol. 18, no 1, 23-30 p.
Keyword [en]
Engraftment, Bandeiraea simplicifolia, Islet graft, Angiogenesis, Pancreas
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96671ISI: 000266055100003PubMedID: 19476206OAI: oai:DiVA.org:uu-96671DiVA: diva2:171321
Available from: 2008-02-01 Created: 2008-02-01 Last updated: 2017-12-14Bibliographically 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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 304
Keyword
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
Identifiers
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
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Available from: 2008-02-01 Created: 2008-02-01Bibliographically approved

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