%0 Journal Article
%T Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia
%A I. K. Hals
%A A. M. Rokstad
%A B. L. Strand
%A J. Oberholzer
%A V. Grill
%J Journal of Diabetes Research
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/374925
%X 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¨C0.3% O2 for 8£¿h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by % in encapsulated and % in nonencapsulated islets ( ). Nonencapsulated islets released 37.7% (median) more HMGB1 compared to encapsulated islets after hypoxic culture conditions ( ). Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by % versus %. 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. 1. Introduction Transplantation of pancreatic islets containing the insulin-producing beta cells could in principle cure type 1 diabetes. However, transplantation of allografts necessitates treatment with immunosuppressant drugs with ensuing side effects. Encapsulation of islets (or isolated beta cells) could potentially alleviate this problem, thus motivating previous and ongoing research on the feasibility of encapsulated islets for successful transplantation. Promising results (reversal of diabetes in animal models of diabetes) have been reported [1¨C4]. However, questions remain as to both the short and long term functionality of encapsulated islets or beta cells. One question pertains to the impact of hypoxia on encapsulated islets. Native pancreatic beta cells have high rates of oxidative metabolism to meet the demand of insulin production and secretion [5], and even moderately decreased levels of oxygen have been shown to inhibit insulin release [6]. Hypoxia after transplantation is a major (albeit not the only) contributor to the dramatic drop of viable beta cells (nonencapsulated) that occurs in the immediate period following transplantation [7¨C10]. A negative impact of the¡ªinevitable¡ªhypoxia during the immediate period following transplantation could possibly be worsened by encapsulation, since the
%U http://www.hindawi.com/journals/jdr/2013/374925/