Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

I K Hals,J Oberholzer,A M Rokstad,B L Strand,V Grill

doi:10.1155/2013/374925

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.

Highlights

Transplantation of pancreatic islets containing the insulinproducing beta cells could in principle cure type 1 diabetes
Nonencapsulated islets released 37.7% more high mobility group box 1 (HMGB1) compared to encapsulated islets after hypoxic culture conditions (P < 0.001)
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

Summary

Introduction

Transplantation of pancreatic islets containing the insulinproducing beta cells could in principle cure type 1 diabetes. Questions remain as to both the short and long term functionality of encapsulated islets or beta cells. 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 [7,8,9,10]. A negative impact of the— inevitable—hypoxia during the immediate period following transplantation could possibly be worsened by encapsulation, since the distance of diffusion for oxygen could be greater in encapsulated versus nonencapsulated islets (or amassed beta cells) [11, 12], and a negative effect of clustering of islets may occur [13]. Comparisons of oxygen uptake in encapsulated versus nonencapsulated islets have been done for neonatal porcine [14] and pig [15] islets in vitro (normoxic conditions)

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Methods

Conclusion