Related Experiment Video
Updated: Jun 16, 2026
Author Spotlight: Investigating Islet Abnormalities and Function with a Pseudoislet Protocol
Published on: November 3, 2023
Identification of Compounds Protecting Pancreatic Islets against Oxidative Stress using a 3D Pseudoislet Screening
Timo Rademakers1, Mireille M J P E Sthijns1,2, Omar Paulino da Silva Filho1
1Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands.
Abstract:
Oxidative stress leads to a lower success rate of clinical islet transplantation. Here, FDA-approved compounds are screened for their potential to decrease oxidative stress and to protect or enhance pancreatic islet viability and function. Studies are performed on in vitro "pseudoislet" spheroids, which are pre-incubated with 1280 different compounds and subjected to oxidative stress. Cell viability and oxidative stress levels are determined using a high-throughput fluorescence microscopy pipeline. Initial screening on cell viability results in 59 candidates. The top ten candidates are subsequently screened for their potential to decrease induced oxidative stress, and eight compounds efficient reduction of induced oxidative stress in both alpha and beta cells by 25-50%. After further characterization, the compound sulfisoxazole is found to be the most capable of reducing oxidative stress, also at short pre-incubation times, which is validated in primary human islets, where low oxidative stress levels and islet function are maintained. This study shows an effective screening strategy with 3D cell aggregates based on cell viability and oxidative stress, which leads to the discovery of several compounds with antioxidant capacity. The top candidate, sulfisoxazole is effective after a 30 min pre-incubation, maintains baseline islet function, and may help alleviate oxidative stress in pancreatic islets.
Insights
This study screened FDA-approved compounds to reduce oxidative stress in pancreatic islets, crucial for transplantation success. Sulfisoxazole emerged as a top candidate, protecting islet viability and function.
Area of Science:
- Endocrinology
- Transplantation Biology
- Drug Discovery
Background:
- Oxidative stress significantly reduces the success rates of clinical islet transplantation.
- Protecting pancreatic islet viability and function is critical for improving transplant outcomes.
Purpose of the Study:
- To screen FDA-approved compounds for their ability to mitigate oxidative stress.
- To identify agents that enhance pancreatic islet viability and function for transplantation.
Main Methods:
- Utilized in vitro "pseudoislet" spheroids for high-throughput screening of 1280 compounds.
- Assessed cell viability and oxidative stress levels using fluorescence microscopy.
- Validated promising compounds, including sulfisoxazole, in primary human islets.
Main Results:
- Identified 59 candidate compounds based on cell viability.
- Eight compounds demonstrated 25-50% reduction in oxidative stress in alpha and beta cells.
- Sulfisoxazole showed significant antioxidant capacity, effective after short pre-incubation, and maintained human islet function.
Conclusions:
- Developed an effective screening strategy using 3D cell aggregates for identifying antioxidant compounds.
- Sulfisoxazole is a promising candidate for reducing oxidative stress in pancreatic islets, potentially improving islet transplantation.
- The identified compounds may offer new therapeutic avenues for enhancing islet transplant success.
