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Author Spotlight: Investigating Islet Abnormalities and Function with a Pseudoislet Protocol
Published on: November 3, 2023
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Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells.
Ishan Goswami1,2, Eleonora de Klerk3, Phichitpol Carnese3
1Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California Berkeley, Berkeley, CA 94720, USA. kehealy@berkeley.edu.
Lab on a Chip
|October 28, 2022
Summary
Developing novel microphysiological systems (MPS) for stem cell-derived beta cells enhances diabetes research and drug discovery. This scalable platform supports high-content, high-throughput screening of beta cell function and drug responses.
Area of Science:
- Biomedical Engineering
- Stem Cell Biology
- Endocrinology
Background:
- Stem cell-derived beta cells are crucial for diabetes research and transplantation, but require advanced culture systems.
- Existing microphysiological systems (MPS) face challenges in scalability and high-throughput application for beta cell research.
- Multi-day culture of stem cell-derived beta cells in MPS remains under-explored.
Purpose of the Study:
- To develop a scalable, multiplexed MPS device for culturing and testing stem cell-derived beta cells.
- To assess the viability and functionality of stem cell-derived beta cell clusters (eBCs) over extended culture periods.
- To demonstrate the utility of the MPS for high-throughput drug screening and metabolic profiling.
Main Methods:
- Engineered a scalable, multiplexed islet beta MPS device with microfluidic gradient generators for parallel fluid handling.
- Cultured stem cell-derived enriched beta clusters (eBCs) within the MPS for one week.
- Assessed eBC viability and function via insulin release in response to glucose challenge and drug exposure (glybenclamide).
- Analyzed metabolic function by measuring insulin secretion in response to metabolites.
Main Results:
- Demonstrated stable viability and functionality of eBCs in the MPS for one week, with a twofold increase in insulin release upon glucose challenge.
- Successfully showed scalable multiplexing for drug testing, observing a reduced stimulation index after long-term glybenclamide exposure.
- Confirmed a glycolytic bottleneck in MPS-cultured eBCs through metabolite-induced insulin secretion responses.
Conclusions:
- The developed MPS platform offers a scalable solution for high-content, high-throughput culture and testing of stem cell-derived beta cells.
- This innovative system supports multi-day culture and functional assessment, advancing biomedical discoveries and drug development for diabetes.
- The platform enables detailed functional and metabolic characterization, paving the way for improved beta cell therapies.
