Co-culture with extracellular matrix proteins reduces hypoxia-induced human islet cell death

Islets are experiencing hypoxic conditions after transplantation. The aim of this study was to assess the effect of collagen IV and laminin isoform -521, -511 and -411 on the survival and function of isolated human islets exposed to severe hypoxia. Compared with hypoxic controls (100%) all ECMs significantly increased islet recovery after culture at 0.75% oxygen ranging from 163 +/- 12% to 173 +/- 28% (P < 0.05) using collagen IV or laminin-411, respectively. Increased post-culture recovery correlated with decreased islet fragmentation which was lowest using laminin-521 (66%, P < 0.01) and laminin-511 (66% P < 0.05). Islet ROS generation was also lowest after culture with laminin-521 and laminin-511. Islet viability was increased in all experimental groups when compared to controls but was highest using collagen IV and laminin-511. This observation corresponds to the insulin response after glucose challenge that was best preserved when collagen IV or laminin-511 was used for islet incubation.