title: Anchoring of vascular endothelial growth factor to surface-immobilized heparin on pancreatic islets: implications for stimulating islet angiogenesis.
abstract: In pancreatic islet transplantation, early revascularization is necessary for long-term graft function. We have shown in in vitro and in vivo models that modification with surface-attached heparin protects the islets from acute attack by the innate immune system of the blood following intraportal islet transplantation. In this study, we have investigated the ability of an immobilized conjugate composed of heparin to bind the angiogenic growth factor vascular endothelial growth factor-A (VEGF-A) as a means of attracting endothelial cells (ECs) to induce angiogenesis and revascularization. We analyzed the capacity of VEGF-A to bind to immobilized heparin and how this affected the proliferation and adherence of ECs to both artificial glass surfaces and islets. Quartz crystal microbalance with dissipation monitoring and slot-blot demonstrated the binding of VEGF-A to heparin-coated surfaces upon which ECs showed protein-dependent proliferation. Also, ECs cultured on heparin-coated glass surfaces exhibited effects upon focal contacts. Heparinized islets combined with VEGF-A demonstrated unaffected insulin release. Further, covering islets with heparin also increased the adhesion of ECs to the islet surface. Immobilized heparin on the islet surface may be a useful anchor molecule for achieving complete coverage of islets with angiogenic growth factors, ultimately improving islet revascularization and engraftment in pancreatic islet transplantation.
authors.affiliation: Division of Clinical Immunology, Department of Oncology, Radiology, and Clinical Immunology, Uppsala University, Uppsala, Sweden.
authors.forename: Sanja
authors.initials: S
authors.lastname: Cabric
authors.forename: Javier
authors.initials: J
authors.lastname: Sanchez
authors.forename: Ulrika
authors.initials: U
authors.lastname: Johansson
authors.forename: Rolf
authors.initials: R
authors.lastname: Larsson
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.forename: Peetra U
authors.initials: PU
authors.lastname: Magnusson
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000098:blood supply* / Q000187:drug effects*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D011791:Quartz; D013499:Surface Properties / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D020099:Coated Materials, Biocompatible; D007328:Insulin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011791:Quartz; D006493:Heparin