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

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 and Jeroen Leijten ()
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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
Gert Jan C. Veenstra: Department of Molecular Developmental Biology
Robert Passier: Department of Applied Stem Cell Technology
Tom Kamperman: Department of Developmental BioEngineering
Jeroen Leijten: Department of Developmental BioEngineering

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42297-0

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