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Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat
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 Medical Cell Biology.
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 Medical Sciences.
2007 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 6, 1257-1266 p.Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis: The few patients subjected to autotransplantation of pancreatic islets after pancreatectomy usually become normoglycaemic after using islets from the resected organ only, whereas allogeneic recipients usually require at least two grafts to retain normoglycaemia. Previous experimental studies have demonstrated that islets transplanted to non-pancreatectomised recipients acquire a markedly decreased blood vessel density, which leads to a hypoxic microenvironment. The aim of the present study was to test the hypothesis that autotransplanted islets have better vascular engraftment and function as a result of the pancreatic surgery involved. Materials and methods: In the present study, athymic mice and inbred rats were subjected to a 60% pancreatectomy and transplanted with human or rat islets, respectively, 4 days later. Control animals underwent sham surgery. Blood flow, oxygen tension, vascular density and endocrine volume in the islet grafts were measured 1 month after transplantation. Separate grafts were used for perfusion experiments and for assessment of beta cell proliferation and endocrine cellular apoptosis at different time periods after transplantation. Results: Islet grafts in partially pancreatectomised recipients had an increased blood flow, oxygen tension, blood vessel density and endocrine mass 1 month post-transplantation compared with control animals. They also exhibited increased insulin release in perfusion experiments performed 1 month post-transplantation, and decreased cellular apoptosis early after transplantation. Conclusions/interpretation: The present study shows that the pancreatectomy procedure itself has beneficial effects on the engraftment of transplanted human and rat islets. Our results provide an additional explanation, besides diminished immunological responses, of the much better outcome of islet autotransplantations compared with allogeneic transplantations in the clinic.

Place, publisher, year, edition, pages
2007. Vol. 50, no 6, 1257-1266 p.
Keyword [en]
Blood flow, Insulin release, Islet graft, Islet transplantation, Oxygen tension, Revascularisation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-94338DOI: 10.1007/s00125-007-0649-5ISI: 000246271600019PubMedID: 17406853OAI: oai:DiVA.org:uu-94338DiVA: diva2:168156
Available from: 2006-04-21 Created: 2006-04-21 Last updated: 2011-02-02Bibliographically approved
In thesis
1. Role of Islet Endothelial Cells in β-cell Function and Growth
Open this publication in new window or tab >>Role of Islet Endothelial Cells in β-cell Function and Growth
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The pancreatic islets are collections of endocrine cells, dispersed throughout the pancreas. In adult islets, endocrine cells are closely associated with capillary endothelial cells and receive a high blood perfusion. Transplanted pancreatic islets, on the other hand, have a vascular disturbance, manifested as decreased blood vessel density. Besides impaired islet blood perfusion and oxygenation, this means that the normal close proximity between endothelial cells and β-cell in adult islets is interrupted. The aim of the thesis was to investigate if, and to what extent, β-cells and islet endothelial cells can interact with one another. This hypothesis was investigated during physiological growth of pancreatic islets, following transplantation and in vitro. We observed that islet endothelial and endocrine cell replication coincided immediately after birth, as well as during pregnancy. In pregnant animals, β-cell proliferation colocalized to islets with increased endothelial cell replication, indicating that the two processes were interconnected. The pregnancy hormone prolactin favored endothelial cell replication, and these activated cells could then augment β-cell proliferation. We found that prolactin pretreatment increased blood vessel density and oxygen tension in islets after transplantation. Furthermore, prolactin pretreatment improved endocrine function in a minimal islet transplant model. Partial pancreatectomy performed in association with islet transplantation improved revascularization, oxygen tension and glucose stimulated insulin release from the graft. In conclusion, the findings suggest that endocrine and endothelial cells interact with one another to regulate growth and function in pancreatic islets. This may form the basis for interventions aiming to improve revascularization and function of transplanted islets.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 57 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 141
Keyword
Cell biology, Cellbiologi
Identifiers
urn:nbn:se:uu:diva-6801 (URN)91-554-6536-6 (ISBN)
Public defence
2006-05-12, Room B:41, BMC, Husargatan 3, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2006-04-21 Created: 2006-04-21 Last updated: 2011-02-02Bibliographically approved

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