title: Intraislet endothelial cells contribute to revascularization of transplanted pancreatic islets.
abstract: Pancreatic islet transplantation is an emerging therapy for type 1 diabetes. To survive and function, transplanted islets must revascularize because islet isolation severs arterial and venous connections; the current paradigm is that islet revascularization originates from the transplant recipient. Because isolated islets retain intraislet endothelial cells, we determined whether these endothelial cells contribute to the revascularization using a murine model with tagged endothelial cells (lacZ knock-in to Flk-1/VEGFR2 gene) and using transplanted human islets. At 3-5 weeks after transplantation beneath the renal capsule, we found that islets were revascularized and that the transplant recipient vasculature indeed contributed to the revascularization process. Using the lacZ-tagged endothelial cell model, we found that intraislet endothelial cells not only survived after transplantation but became a functional part of revascularized islet graft. A similar contribution of intraislet endothelial cells was also seen with human islets transplanted into an immunodeficient mouse model. In the murine model, individual blood vessels within the islet graft consisted of donor or recipient endothelial cells or were a chimera of donor and recipient endothelial cells, indicating that both sources of endothelial cells contribute to the new vasculature. These observations suggest that interventions to activate, amplify, or sustain intraislet endothelial cells before and after transplantation may facilitate islet revascularization, enhance islet survival, and improve islet transplantation.
authors.affiliation: Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Marcela
authors.initials: M
authors.lastname: Brissova
authors.forename: Michael
authors.initials: M
authors.lastname: Fowler
authors.forename: Peter
authors.initials: P
authors.lastname: Wiebe
authors.forename: Alena
authors.initials: A
authors.lastname: Shostak
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shiota
authors.forename: Aramandla
authors.initials: A
authors.lastname: Radhika
authors.forename: P Charles
authors.initials: PC
authors.lastname: Lin
authors.forename: Maureen
authors.initials: M
authors.lastname: Gannon
authors.forename: Alvin C
authors.initials: AC
authors.lastname: Powers
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000032:analysis; D002470:Cell Survival; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000098:blood supply* / Q000378:metabolism; D007668:Kidney / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018919:Neovascularization, Physiologic; D010179:Pancreas / Q000378:metabolism; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D040301:Vascular Endothelial Growth Factor Receptor-2