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

• Published in: PloS one 2022-03, Vol.17 (3), p.e0257578-e0257578
• Main Authors: Sthijns, Mireille M J P E, Rademakers, Timo, Oosterveer, Jolien, Geuens, Thomas, van Blitterswijk, Clemens A, LaPointe, Vanessa L S
• Format: Article
• Language: English
• Subjects: Aggregates; Antioxidants; Antioxidants - metabolism; Beta cells; Bioengineering; Biology; Biology and Life Sciences; Cell culture; Cell death; Cell lines; Cell survival; Chemical compounds; Coculture Techniques; Composition; Glutathione; Health aspects; Hydrogen; Hydrogen peroxide; Insulin-Secreting Cells - metabolism; Islets of Langerhans; Islets of Langerhans - metabolism; Medicine; Medicine and Health Sciences; Metabolism; Monolayers; Oxidation resistance; Oxidative Stress; Pancreas; Pharmaceuticals; Physical Sciences; Physiology; Ratios; Research and Analysis Methods; Stem cell transplantation; Therapeutic applications; Tissue engineering
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0257578

The pancreatic islets of Langerhans have low endogenous antioxidant levels and are thus especially sensitive to oxidative stress, which is known to influence cell survival and behaviour. As bioengineered islets are gaining interest for therapeutic purposes, it is important to understand how their composition can be optimized to diminish oxidative stress. We investigated how the ratio of the two main islet cell types (alpha and beta cells) and their culture in three-dimensional aggregates could protect against oxidative stress. Monolayer and aggregate cultures were established by seeding the alphaTC1 (alpha) and INS1E (beta) cell lines in varying ratios, and hydrogen peroxide was applied to induce oxidative stress. Viability, oxidative stress, and the level of the antioxidant glutathione were measured. Both aggregation and an increasing prevalence of INS1E cells in the co-cultures conferred greater resistance to cell death induced by oxidative stress. Increasing the prevalence of INS1E cells also decreased the number of alphaTC1 cells experiencing oxidative stress in the monolayer culture. In 3D aggregates, culturing the alphaTC1 and INS1E cells in a ratio of 50:50 prevented oxidative stress in both cell types. Together, the results of this study lead to new insight into how modulating the composition and dimensionality of a co-culture can influence the oxidative stress levels experienced by the cells.