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Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia
journal contributionposted on 2016-04-04, 00:00 authored by I. K. Hals, A. M. Rokstad, B. L. Strand, J. Oberholzer, V. Grill
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.
The authors are grateful to Kari Slørdahl for performing DNA quantifications and to Liv Ryan for performing multiplex analysis. I. K. Hals, A. M. Rokstad, and B. L. Strand are supported by Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU). J. Oberholzer is supported by the Chicago Project and NIH Grant R01 DK091526-01A1. V. Grill has received support from the Norwegian Diabetes Association.
PublisherHindawi Publishing Corporation