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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.

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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.

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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.