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Increased Numbers of Low-Oxygenated Pancreatic Islets After Intraportal Islet Transplantation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
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.
2011 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, no 9, 2350-2353 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE-No previous study has measured the oxygenation of intraportally transplanted islets, although recent data suggest that insufficient engraftment may result in hypoxia and loss of islet cells. RESEARCH DESIGN AND METHODS-After intraportal infusion into syngeneic mice, islet oxygenation was investigated in 1-day-old, 1-month-old, or 3-month-old grafts and compared with renal subcapsular grafts and native islets. Animals received an intravenous injection of pimonidazole for immunohistochemical detection of low-oxygenated islet cells (pO(2) <10 mmHg), and caspase-3 immunostaining was performed to assess apoptosis rates in adjacent tissue sections. RESULTS-In the native pancreas of nontransplanted animals, similar to 30% of the islets stained positive for pimonidazole. In 1-day-old and 1-month-old grafts, the percentage of pimonidazole-positive islets in the liver was twice that of native islets, whereas this increase was abolished in 3-month-old grafts. Beneath the renal capsule, pimonidazole accumulation was, however, similar to native islets at all time points. Apoptosis rates were markedly increased in 1-day-old intrahepatic grafts compared with corresponding renal islet grafts, which were slightly increased compared with native islets. One month posttransplantation renal subcapsular grafts had similar frequencies of apoptosis as native islets, whereas apoptosis in intraportally implanted islets was still high. In the liver, islet graft vascular density increased between 1 and 3 months posttransplantation, and apoptosis rates simultaneously dropped to values similar to those observed in native islets. CONCLUSIONS-The vascular engraflment of intraportally transplanted islets is markedly delayed compared with renal islet grafts. The prolonged ischemia of intraportally transplanted islets may favor an alternative implantation site.

Place, publisher, year, edition, pages
2011. Vol. 60, no 9, 2350-2353 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-159242DOI: 10.2337/db09-0490ISI: 000294699600018OAI: oai:DiVA.org:uu-159242DiVA: diva2:443844
Available from: 2011-09-27 Created: 2011-09-26 Last updated: 2017-12-08Bibliographically approved

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Centrum för klinisk forskning i Sörmland (CKFD)Clinical ImmunologyDepartment of Medical Cell BiologyDepartment of Medical Sciences
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