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.

Extracellular hemoglobin combined with an O2‐generating material overcomes O2 limitation in the bioartificial pancreas

“…Nevertheless, we showed that low oxygen tension significantly damages NPI function, metabolism and viability from 2 to 7 days of culture. In keeping with the literature describing the impact of ischemia or hypoxia on human pancreatic islets (Brandhorst et al, ; Cantley et al, ; Giuliani et al, ; Hals, Rokstad, Strand, Oberholzer & Grill, ; Lai et al, ; Moritz et al, ), our results suggest that the innovative oxygen supply strategy developed in the present study may also meet the challenges of hypoxia during allotransplantation of macroencapsulated human pancreatic islets.…”

Current and Future Perspectives on Alginate Encapsulated Pancreatic Islet

“…Hence, lack of vascularization and potential hypoxia is also an issue without capsules, however with capsules the potential ingrowth of blood vessels into the islets is physically hindered by the capsule. For short‐term (acute) hypoxia in vitro, no difference on viability or function was seen for encapsulated versus nonencapsulated human islets . However, culture of encapsulated islets under low oxygen conditions shows loss of viable tissue and necrotic cores .…”

Culture of hESC‐derived pancreatic progenitors in alginate‐based scaffolds

“…On the other hand, our recent experience with culture of human islets in capsules of similar size (450-500 µm) points towards a protective role of the alginate hydrogel for encapsulated tissue when cultured under limited oxygen supply [49].…”