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.

The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress

“…In summary, increasing the number of INS1E cells in a monolayer co-culture led to more resistance to decreases in viability induced by oxidative stress, whereas the viability was the highest in 3D aggregates comprising 50% and 80% INS1E cells (Fig 1 Our finding that H2O2 decreased the viability of INS1E is consistent with other studies [23,29,30], as is our result that 3D aggregation protected against an oxidative stress-induced decrease in viability [31,32]. Overall, the oxidative stress the cells experienced did not correspond to their viability, which is not unexpected [33].…”

Antioxidant and anti-diabetic effects of caffeic acid in a rat model of diabetes

“…However, when the diabetic rats were treated with caffeic acid, there were significant decreases in fasting blood glucose levels, most likely due to the enhancement of insulin levels. The increase in insulin might have resulted from increased insulin secretion from pancreas and/or regeneration of pancreatic β-cells, as has been proposed in previous studies [12,13]. Similar anti-diabetic effects have been observed for caffeic acid esters in previous reports [14].…”

The Role of Pancreatic Alpha Cells and Endothelial Cells in the Reduction of Oxidative Stress in Pseudoislets

“…As far as improving the protective effect of endothelial cells against oxidative stress, many non-enzymatic compounds, such as vitamin C, d -α-tocopherol (vitamin E), glutathione and α-lipoic acid, have been supplemented to cells in in vitro and in vivo studies with a conclusive reduction in oxidative stress ( Matough et al, 2012 ; Myasnikova et al, 2019 ). In our approach, we relied on the self-assembly process that forms the pseudoislet.…”

“…The pancreatic tissue is one of the most metabolically active tissues within the human body, and especially the β cells at elevated glucose concentrations rely on oxidative metabolism for adenosine triphosphate synthesis ( Bakker et al, 2000 ). To illustrate this, the islets of Langerhans receive up to 10% of the pancreas’ blood supply, but only occupy 1–2% of its volume ( Myasnikova et al, 2019 ).…”