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Updated: Jul 26, 2025
Differentiation of Human Pluripotent Stem Cells Into Pancreatic Beta-Cell Precursors in a 2D Culture System
Published on: December 16, 2021
Harnessing Human Pluripotent Stem Cell-Derived Pancreatic In Vitro Models for High-Throughput Toxicity Testing and
Carmen Ching1,2,3, Elhadi Iich1,2, Adrian Kee Keong Teo4,5,6,7
1Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Abstract:
The long-standing goals in diabetes research are to improve β-cell survival, functionality and increase β-cell mass. Current strategies to manage diabetes progression are still not ideal for sustained maintenance of normoglycemia, thereby increasing demand for the development of novel drugs. Available pancreatic cell lines, cadaveric islets, and their culture methods and formats, either 2D or 3D, allow for multiple avenues of experimental design to address diverse aims in the research setting. More specifically, these pancreatic cells have been employed in toxicity testing, diabetes drug screens, and with careful curation, can be optimized for use in efficient high-throughput screenings (HTS). This has since spearheaded the understanding of disease progression and related mechanisms, as well as the discovery of potential drug candidates which could be the cornerstone for diabetes treatment. This book chapter will touch on the pros and cons of the most widely used pancreatic cells, including the more recent human pluripotent stem cell-derived pancreatic cells, and HTS strategies (cell models, design, readouts) that can be used for the purpose of toxicity testing and diabetes drug discovery.
Insights
Developing new diabetes drugs requires improving beta-cell function and mass. This review explores pancreatic cell models and high-throughput screening (HTS) strategies for effective toxicity testing and drug discovery.
Area of Science:
- Endocrinology and Metabolism
- Cell Biology
- Pharmacology
Background:
- Diabetes research aims to enhance beta-cell survival, function, and mass.
- Current diabetes management strategies have limitations in maintaining normoglycemia, necessitating novel drug development.
- Pancreatic cell models are crucial for understanding disease mechanisms and discovering therapeutic candidates.
Purpose of the Study:
- To review pancreatic cell models for diabetes research.
- To discuss high-throughput screening (HTS) strategies for drug discovery and toxicity testing.
- To evaluate the advantages and disadvantages of various pancreatic cell types, including stem cell-derived models.
Main Methods:
- Review of existing literature on pancreatic cell culture and HTS.
- Analysis of different pancreatic cell lines, cadaveric islets, and stem cell-derived pancreatic cells.
- Examination of 2D and 3D cell culture formats for experimental design.
- Evaluation of HTS strategies, including assay design and readouts for toxicity testing and drug screening.
Main Results:
- Various pancreatic cell models (cell lines, islets, stem cell-derived) offer distinct advantages for diabetes research.
- High-throughput screening (HTS) enables efficient toxicity testing and the discovery of potential diabetes drugs.
- Optimization of cell models and HTS protocols is key for successful drug discovery and understanding disease progression.
Conclusions:
- Pancreatic cell models and HTS are indispensable tools for advancing diabetes research and drug development.
- Human pluripotent stem cell-derived pancreatic cells represent a promising avenue for future studies.
- Effective utilization of these models can accelerate the discovery of novel diabetes therapeutics.
