title: Beneficial role of pancreatic microenvironment for angiogenesis in transplanted pancreatic islets.
abstract: Pancreatic islets implanted heterotopically (i.e., into the kidney, spleen, or liver) become poorly revascularized following transplantation. We hypothesized that islets implanted into the pancreas would become better revascularized. Islets isolated from transgenic mice expressing enhanced yellow fluorescent protein (EYFP) in all somatic cells were cultured before they were implanted into the pancreas or beneath the renal capsule of athymic mice. Vascular density was evaluated in histological sections 1 month posttransplantation. EYFP was used as reporter for the transgene to identify the transplanted islets. Islet endothelial cells were visualized by staining with the lectin Bandeiraea simplicifolia (BS-1). Capillary numbers in intrapancreatically implanted islets were only slightly lower than those counted in endogenous islets, whereas islets implanted beneath the renal capsule had a markedly lower vascular density. In order to determine if this high graft vascular density at the intrapancreatic site reflected expansion of remnant donor endothelial cells or increased ingrowth of blood vessels from the host, also islets from Tie2-green fluorescent protein (GFP) mice (i.e., islets with fluorescent endothelial cells) were transplanted into the pancreas or beneath the renal capsule of athymic mice. These islet grafts revealed that the new vascular structures formed in the islet grafts contained very few GFP-positive cells, and thus mainly were of recipient origin. The reason(s) for the much better ingrowth of blood vessels at the intrapancreatic site merits further studies, because this may help us form strategies to overcome the barrier for ingrowth of host vessels also into islets in heterotopic implantation sites.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Joey.Lau@mcb.uu.se
authors.forename: Joey
authors.initials: J
authors.lastname: Lau
authors.forename: Caroline
authors.initials: C
authors.lastname: Kampf
authors.forename: Göran
authors.initials: G
authors.lastname: Mattsson
authors.forename: Daniel
authors.initials: D
authors.lastname: Nyqvist
authors.forename: Martin
authors.initials: M
authors.lastname: Köhler
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Carlsson
mesh_terms: D000818:Animals; D042783:Endothelial Cells; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000098:blood supply* / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008164:Luminescent Proteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology
chemical_list: D008164:Luminescent Proteins