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Low Revascularization of Experimentally Transplanted Human Pancreatic Islets

Departments of Medical Cell Biology (P.-O.C., F.P., G.M.) and Diagnostic Radiology (F.P.), Uppsala University, SE-751 23 Uppsala, Sweden

Address all correspondence and requests for reprints to: Per-Ola Carlsson, M.D., Ph.D., Department of Medical Cell Biology, Biomedical Center, Husargatan 3, Box 571, SE-751 23 Uppsala, Sweden. E-mail: per-ola.carlsson{at}medcellbiol.uu.se.

Abstract

Pancreatic islets are avascular immediately after transplantation. Although the islets are rapidly revascularized, it is uncertain whether the revascularization produces an adequate oxygenation of the transplanted islet tissue. We measured pO₂, blood flow and vascular density in mouse or human islets 1 month after transplantation to nude mice. Tissue pO₂ was measured with Clark microelectrodes. Blood perfusion was measured with laser-Doppler flow cytometry, whereas vascular density was determined in histological specimens stained for the lectin Bandeiraea simplicifolia (BS-1). Both the transplanted mouse and human islets had a pO₂ 15–20% of that in endogenous mouse islets. Moreover, the vascular density of the transplanted islets was decreased compared with that of endogenous mouse and human islets. Graft blood perfusion was approximately 50% of renal cortex blood flow. A negative correlation was found between donor age and blood perfusion of the human islet grafts. A similar correlation was seen between donor age and the total vascular density of these grafts. In conclusion, transplanted human islets had a markedly decreased vascular density and pO₂ compared with endogenous islets. This has potential implications for clinical islet transplantations, because poor vascular engraftment may significantly increase the number of islets needed to obtain insulin independence.

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