Synergic effects of oxygen supply and antioxidants on pancreatic β-cell spheroids

Abstract

Diabetes is one of the most common metabolic disorders, and is characterized by the inability to secrete/sense insulin and abnormal blood glucose concentration. Many researchers have concentrated their efforts on improving islet transplantation, in particular by fabricating bioartificial pancreatic islets in vitro. One of the critical points for the success of this research direction is the improvement of culture conditions, such as oxygen supply, in the engineering of bioartificial pancreatic islets to ensure their viability and functionality after transplantation. In this work, we fabricated microwell spheroid culture devices made of oxygen-permeable polydimethylsiloxane (PDMS), with which hypoxia in the core of bioartificial islets was alleviated and glucose-stimulated insulin secretion was increased ~2.5-fold compared to a device with the same configuration but made of non-oxygen-permeable plastic. We also demonstrated that antioxidants, such as ascorbic acid-2-phosphate (AA2P), could neutralize islet damage caused by increased reactive oxygen species (ROS) in the cell culture environment. These results suggest that supply of oxygen together with removal of ROS may lead to a better approach to prepare highly viable and functional bioartificial pancreatic islets.