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Prolactin treatment improves engraftment and function of transplanted pancreatic islets
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. (Per-Ola Carlsson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. (Per-Ola Carlsson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. (Leif Jansson)
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, Internal Medicine. (Per-Ola Carlsson)
2009 (English)In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 150, no 4, 1646-1653 p.Article in journal (Refereed) Published
Abstract [en]

Transplantation of pancreatic islets is clinically used to treat type 1 diabetes, but requires multiple donors. Previous experimental studies have demonstrated that transplanted islets have a low blood vessel density, which leads to a hypoxic microenvironment. The present study tested the hypothesis that experimental prolactin pretreatment, a substance which seems to stimulate angiogenesis in endogenous islets, would increase graft blood vessel density, thereby improving transplantation outcome. Pancreatic islets from C57BL/6 mice were incubated with prolactin (500 ng/ml) or vehicle during the last 24 h of culture before syngeneic transplantation beneath the renal capsule, or recipients were injected with prolactin or vehicle for the first 7 days after transplantation. One month post-transplantation, graft vascular density, blood flow, oxygen tension, endocrine volume and function was evaluated. Also human islets were incubated with prolactin or vehicle before experimental transplantation and investigated for vascular engraftment. Vascular engraftment of syngeneically transplanted mouse islets was improved by both in vivo and in vitro prolactin pretreatment. Moreover, prolactin pretreatment in vitro of islets used for transplantation improved recovery from diabetes in a minimal islet mass model. Interestingly, also human islets subjected to prolactin treatment before experimental transplantation demonstrated improved revascularization, blood perfusion and oxygen tension when evaluated one month post-transplantation. We conclude that prolactin may improve engraftment of transplanted pancreatic islets. The protocol with pretreatment of islets ex vivo could minimize the risk of side effects when used in the clinical setting.

Place, publisher, year, edition, pages
2009. Vol. 150, no 4, 1646-1653 p.
Keyword [en]
Angiogenesis, Islet graft, Islet of Langerhans, Prolactin, Thrombospondin-1
National Category
Medical and Health Sciences
Research subject
Medical Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-98718DOI: 10.1210/en.2008-1318ISI: 000264442900012PubMedID: 19095742OAI: oai:DiVA.org:uu-98718DiVA: diva2:207345
Available from: 2009-03-10 Created: 2009-03-02 Last updated: 2017-12-13Bibliographically 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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