title: Co-transplantation of endothelial progenitor cells and pancreatic islets to induce long-lasting normoglycemia in streptozotocin-treated diabetic rats.
abstract: Graft vascularization is a crucial step to obtain stable normoglycemia in pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute to neoangiogenesis and to the revascularization process during ischaemic events and play a key role in the response to pancreatic islet injury. In this work we co-transplanted EPCs and islets in the portal vein of chemically-induced diabetic rats to restore islet vascularization and to improve graft survival. Syngenic islets were transplanted, either alone or with EPCs derived from green fluorescent protein (GFP) transgenic rats, into the portal vein of streptozotocin-induced diabetic rats. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests were performed. Real time-PCR was carried out to evaluate the gene expression of angiogenic factors. Diabetic-induced rats showed long-lasting (6 months) normoglycemia upon co-transplantation of syngenic islets and EPCs. After 3-5 days from transplantation, hyperglycaemic levels dropped to normal values and lasted unmodified as long as they were checked. Further, glucose tolerance tests revealed the animals' ability to produce insulin on-demand as indexed by a prompt response in blood glucose clearance. Graft neovascularization was evaluated by immunohistochemistry: for the first time the measure of endothelial thickness revealed a donor-EPC-related neovascularization supporting viable islets up to six months after transplant. Our results highlight the importance of a newly formed viable vascular network together with pancreatic islets to provide de novo adequate supply in order to obtain enduring normoglycemia and prevent diabetes-related long-term health hazards.
authors.affiliation: Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Quaranta
authors.affiliation: Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Antonini
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Saturnino
authors.initials: S
authors.lastname: Spiga
authors.affiliation: Department of Clinical and Experimental Medicine, Haematology Section, University of Florence, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzanti
authors.affiliation: U.O. Immunohaematology, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Curcio
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mulas
authors.affiliation: Department of Chemistry and Pharmacy, "G. Minardi" Laboratory of Cognitive Neuroscience, University of Sassari, Sassari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Diana
authors.affiliation: Department of Computer Science, University of Verona, Verona, Italy.
authors.forename: Pasquina
authors.initials: P
authors.lastname: Marzola
authors.affiliation: Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Mosca
authors.affiliation: Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy.
authors.forename: Biancamaria
authors.initials: B
authors.lastname: Longoni
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000637:transplantation*; D005786:Gene Expression Regulation; D006943:Hyperglycemia / Q000150:complications / Q000628:therapy; D016381:Islets of Langerhans Transplantation; D008099:Liver / Q000473:pathology; D008297:Male; D018919:Neovascularization, Physiologic / Q000235:genetics; D010179:Pancreas / Q000473:pathology; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D013311:Streptozocin; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D013311:Streptozocin
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