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Transplantation of pancreatic islets reconstitutes glucose homeostasis in diabetes mellitus. Before transplantation, islets are disrupted from the surrounding blood vessels by the isolation procedure, with the grafted tissue being subject to ischemic damage. The survival of transplanted islets is assumed to depend on effective revascularization. Perfusion studies suggest that newly formed microvessels supplying the graft with nutrients are exclusively rebuilt by the host. It is generally not known whether isolated islets contain endothelial cells (EC), which potentially participate in the revascularization process. Therefore, we tried to detect immature EC in isolated islets by transformation with polyoma middle T antigen. Endothelioma cells were generated, implicating the presence of de-differentiated EC within isolated islets. When embedded in a fibrin gel, the islets developed cellular cords consisting of EC, whereas FGF-2 and VEGF stimulated the formation of cord-like structures. Furthermore, we studied the presence of donor EC in islet grafts by using transgenic mice with an EC lineage-specific promotor-LacZ reporter construct (Tie-2LacZ). Following islet transplantation, Tie-2LacZ-positive EC of both donor and recipient were identified in the vicinity of or within the graft up to 3 wk after transplantation. In conclusion, EC and/or their progenitors with angiogenic capacity reside within isolated islets of different species, and their proliferative potential can be stimulated by various inducers. These graft-related endothelia persist after islet transplantation and are integrated within newly formed microvessels.

Original publication

DOI

10.1096/fj.02-0615fje

Type

Journal article

Journal

FASEB J

Publication Date

05/2003

Volume

17

Pages

881 - 883

Keywords

Animals, Cell Division, Cell Hypoxia, Endothelial Growth Factors, Endothelium, Vascular, Fibroblast Growth Factors, Glucose, Humans, Intercellular Signaling Peptides and Proteins, Islets of Langerhans, Islets of Langerhans Transplantation, Lac Operon, Lymphokines, Mice, Mice, Transgenic, Neovascularization, Physiologic, Rats, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, von Willebrand Factor