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Experimental Studies on the Vasculature of Endogenous and Transplanted Islets of Langerhans
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The blood vessels of the pancreatic islets are of crucial importance for oxygen and metabolite supply as well as dispersal of secreted hormones. In addition to this, endothelial cells have an important role in the revascularization process after islet transplantation. Previous studies have reported signs of poor engraftment of transplanted islets, presumably due to impaired revascularization. The aims of this thesis were to investigate the revascularization process of transplanted islets and to examine the role of islet endothelial cells. In this context, the lectin Bandeiraea simplicifolia was found to stain endothelium of both endogenous and transplanted pancreatic islets. By using this lectin we investigated the vascular density of both endogenous and islets transplanted syngeneically beneath the renal capsule, into the spleen or intraportally into the liver of normoglycemic C57BL/6 mice. One month post-transplantation, a time point when the grafts are assumed to be completely revascularized, the vascular density was decreased at all three implantation sites when compared to endogenous islets. Furthermore, most of the blood vessels were located in the graft connective tissue stroma. Similar results were obtained when islet transplant vascular density was determined six months post-transplantation and in cured diabetic animals after one month. In order to evaluate the function of intraportally transplanted islets, we developed a method to retrieve such islets. We treated the implantation organ (liver) first enzymatically (collagenase) and then mechanically, thereafter we could re-isolate the transplanted islets for further in vitro studies. The retrieved islets had a decreased insulin relase, insulin content and glucose oxidation rate when compared to non-transplanted control islets. To understand the role of islet endothelium in the revascularization of transplanted islets we performed angiogenesis GEArray studies on islet endothelial cells, from non-cultured, cultured and transplanted islets. We found that the islet endothelium expressed mRNA for both inhibitors and inducers of angiogenesis, and that this expression differed with time. The functional consequences of this remain to be determined. In summary, the results presented above provide a useful platform for future studies of the morphology and function of islet endothelial cells, especially with a view for elucidating changes induced by islet transplantation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2003. , p. 34
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1290
Keywords [en]
Medicine, islets of Langerhans, endothelial cells, islet transplantation, vascular density, diabetes mellitus
Keywords [sv]
Medicin
National Category
Dermatology and Venereal Diseases
Identifiers
URN: urn:nbn:se:uu:diva-3596ISBN: 91-554-5749-5 (print)OAI: oai:DiVA.org:uu-3596DiVA, id: diva2:163381
Public defence
2003-10-25, B21, Biomedicinskt centrum BMC, Uppsala, 10:15
Opponent
Supervisors
Available from: 2003-10-01 Created: 2003-10-01Bibliographically approved
List of papers
1. Histological markers for endothelial cells in endogenous and transplanted rodent pancreatic islets
Open this publication in new window or tab >>Histological markers for endothelial cells in endogenous and transplanted rodent pancreatic islets
2002 In: Pancreatology, ISSN 1424-3903, Vol. 2, no 2, p. 155-162Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90870 (URN)
Available from: 2003-10-01 Created: 2003-10-01Bibliographically approved
2. Decreased vascular density in mouse pancreatic islets after transplantation
Open this publication in new window or tab >>Decreased vascular density in mouse pancreatic islets after transplantation
2002 In: Diabetes, ISSN 0012-1797, Vol. 51, no 5, p. 1362-1366Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90871 (URN)
Available from: 2003-10-01 Created: 2003-10-01Bibliographically approved
3. Impaired revascularization of transplanted mouse pancreatic islets is chronic and glucose-independent
Open this publication in new window or tab >>Impaired revascularization of transplanted mouse pancreatic islets is chronic and glucose-independent
2003 In: Transplantation, ISSN 0041-13337, Vol. 75, no 5, p. 736-739Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90872 (URN)
Available from: 2003-10-01 Created: 2003-10-01Bibliographically approved
4. Evidence of functional impairment of syngeneically transplanted mouse pancreatic islets retrieved from the liver
Open this publication in new window or tab >>Evidence of functional impairment of syngeneically transplanted mouse pancreatic islets retrieved from the liver
Show others...
Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-90873 (URN)
Available from: 2003-10-01 Created: 2003-10-01Bibliographically approved
5. Endothelial cells in endogenous and transplanted pancreatic islets: differences in the expression of angiogenic peptides and receptors
Open this publication in new window or tab >>Endothelial cells in endogenous and transplanted pancreatic islets: differences in the expression of angiogenic peptides and receptors
Show others...
2006 (English)In: Pancreatology (Print), ISSN 1424-3903, E-ISSN 1424-3911, Vol. 6, no 1-2, p. 86-95Article in journal (Refereed) Published
Abstract [en]

Background/Aims: An important reason for the large amount of islets required for successful islet transplantation is likely to be inadequate engraftment of the transplanted islets. Thus, the revascularization is of major importance for graft survival. In order to study the expression of angiogenic peptides and receptors on islet endothelial cells (EC), we needed methods giving access to such endothelium. Therefore, we developed methods to isolate EC from islets transplanted intraportally or beneath the kidney capsule. Methods: Pancreatic islets were isolated, cultured and syngeneically transplanted into the liver or beneath the kidney capsule of C57BL/6 mice. One month post-transplantation, the islets were retrieved and EC from these islets were explanted. EC were also collected from freshly isolated and cultured non-transplanted islets. The EC were purified with Dynabeads and identified with immunocytochemistry. Angiogenesis GEArray technology was used to study angiogenic gene expression. Results: Several angiogenic genes were expressed in EC; e. g. endostatin, pigment-epithelial derived factor, vascular endothelial growth factor and angiopoietin-2, and their expression were affected by culture. Conclusion: The expression of angiogenesis-related genes in islet EC from non-transplanted islets is affected by culture. Moreover, we also describe a technique, which makes it possible to obtain EC from transplanted islets.

Keywords
Animals, Cells; Cultured, Endothelial Cells/metabolism/*physiology, Immunohistochemistry, Islets of Langerhans/*cytology/metabolism, Islets of Langerhans Transplantation/*physiology, Kidney/metabolism/pathology, Liver/metabolism/pathology, Male, Mice, Mice; Inbred C57BL, Neovascularization; Pathologic/*metabolism/pathology, Peptide Hormones/*physiology, Plant Lectins, RNA/biosynthesis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-90874 (URN)10.1159/000090027 (DOI)000244256700012 ()
Available from: 2003-10-01 Created: 2003-10-01 Last updated: 2017-12-14Bibliographically approved

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