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Mass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules

Author

Listed:
  • Bas Loo

    (Department of Developmental BioEngineering)

  • Simone A. Den

    (Department of Applied Stem Cell Technology)

  • Nuno Araújo-Gomes

    (Department of Developmental BioEngineering)

  • Vincent Jong

    (Department of Developmental BioEngineering)

  • Rebecca R. Snabel

    (Department of Molecular Developmental Biology)

  • Maik Schot

    (Department of Developmental BioEngineering)

  • José M. Rivera-Arbeláez

    (Department of Applied Stem Cell Technology
    BIOS Lab-on-a-Chip Group)

  • Gert Jan C. Veenstra

    (Department of Molecular Developmental Biology)

  • Robert Passier

    (Department of Applied Stem Cell Technology
    Department of Anatomy and Embryology)

  • Tom Kamperman

    (Department of Developmental BioEngineering
    IamFluidics B.V.)

  • Jeroen Leijten

    (Department of Developmental BioEngineering)

Abstract

Organoids are engineered 3D miniature tissues that are defined by their organ-like structures, which drive a fundamental understanding of human development. However, current organoid generation methods are associated with low production throughputs and poor control over size and function including due to organoid merging, which limits their clinical and industrial translation. Here, we present a microfluidic platform for the mass production of lumenogenic embryoid bodies and functional cardiospheres. Specifically, we apply triple-jet in-air microfluidics for the ultra-high-throughput generation of hollow, thin-shelled, hydrogel microcapsules that can act as spheroid-forming bioreactors in a cytocompatible, oil-free, surfactant-free, and size-controlled manner. Uniquely, we show that microcapsules generated by in-air microfluidics provide a lumenogenic microenvironment with near 100% efficient cavitation of spheroids. We demonstrate that upon chemical stimulation, human pluripotent stem cell-derived spheroids undergo cardiomyogenic differentiation, effectively resulting in the mass production of homogeneous and functional cardiospheres that are responsive to external electrical stimulation. These findings drive clinical and industrial adaption of stem cell technology in tissue engineering and drug testing.

Suggested Citation

  • Bas Loo & Simone A. Den & Nuno Araújo-Gomes & Vincent Jong & Rebecca R. Snabel & Maik Schot & José M. Rivera-Arbeláez & Gert Jan C. Veenstra & Robert Passier & Tom Kamperman & Jeroen Leijten, 2023. "Mass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42297-0
    DOI: 10.1038/s41467-023-42297-0
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