title: Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia.
abstract: Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1-0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8 ± 3.5% in encapsulated and 42.9 ± 5.2% in nonencapsulated islets (P < 0.2). Nonencapsulated islets released 37.7% (median) more HMGB1 compared to encapsulated islets after hypoxic culture conditions (P < 0.001). Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by 22.0 ± 6.1% versus 24.8 ± 5.7%. Among 27 tested cytokines/chemokines, hypoxia increased the secretion of IL-6 and IL-8/CXCL8 in both groups of islets, whereas an increase of MCP-1/CCL2 was seen only with nonencapsulated islets. Conclusion. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Postbox 8905, 7491 Trondheim, Norway.
authors.forename: I K
authors.initials: IK
authors.lastname: Hals
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Postbox 8905, 7491 Trondheim, Norway.
authors.forename: A M
authors.initials: AM
authors.lastname: Rokstad
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Postbox 8905, 7491 Trondheim, Norway ; Department of Biotechnology, Faculty of Natural Sciences and Technology, Norwegian University of Science and Technology, 7034 Trondheim, Norway.
authors.forename: B L
authors.initials: BL
authors.lastname: Strand
authors.affiliation: Department of Surgery, University of Illinois, IL at Chicago, Chicago, IL 60612, USA.
authors.forename: J
authors.initials: J
authors.lastname: Oberholzer
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Postbox 8905, 7491 Trondheim, Norway ; Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Postbox 3250, 7006 Trondheim, Norway.
authors.forename: V
authors.initials: V
authors.lastname: Grill
mesh_terms: D000328:Adult; D000464:Alginates; D015687:Cell Hypoxia; D002470:Cell Survival; D004339:Drug Compounding; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008863:Microspheres; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D014019:Tissue Donors
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D007328:Insulin; D020723:Glucuronic Acid; D010100:Oxygen