A microfluidic platform integrating functional vascularized organoids-on-chip

Clément Quintard, Emily Tubbs, Gustav Jonsson, Jie Jiao, Jun Wang, Nicolas Werschler, Camille Laporte, Amandine Pitaval, Thierno-Sidy Bah, Gideon Pomeranz, Caroline Bissardon, Joris Kaal, Alexandra Leopoldi, David A. Long, Pierre Blandin, Jean-Luc Achard, Christophe Battail, Astrid Hagelkruys, Fabrice Navarro, Yves Fouillet, Josef M. Penninger () and Xavier Gidrol ()
Additional contact information
Clément Quintard: Univ. Grenoble Alpes, CEA, IRIG/BGE, BIOMICS
Emily Tubbs: Univ. Grenoble Alpes, CEA, IRIG/BGE, BIOMICS
Gustav Jonsson: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, IMBA
Jie Jiao: University of British Columbia
Jun Wang: University of British Columbia
Nicolas Werschler: University of British Columbia
Camille Laporte: Univ. Grenoble Alpes, CEA, IRIG/BGE, BIOMICS
Amandine Pitaval: Univ. Grenoble Alpes, CEA, IRIG/BGE, BIOMICS
Thierno-Sidy Bah: Univ. Grenoble Alpes, CEA, IRIG, BGE, Gen&Chem
Gideon Pomeranz: UCL Great Ormond Street Institute of Child Health
Caroline Bissardon: Univ. Grenoble Alpes, CEA, LETI, DTBS
Joris Kaal: Univ. Grenoble Alpes, CEA, LETI, DTBS
Alexandra Leopoldi: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, IMBA
David A. Long: UCL Great Ormond Street Institute of Child Health
Pierre Blandin: Univ. Grenoble Alpes, CEA, LETI, DTBS
Jean-Luc Achard: Université Grenoble Alpes, CNRS, Grenoble INP, LEGI
Christophe Battail: Univ. Grenoble Alpes, CEA, IRIG, BGE, Gen&Chem
Astrid Hagelkruys: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, IMBA
Fabrice Navarro: Univ. Grenoble Alpes, CEA, LETI, DTBS
Yves Fouillet: Univ. Grenoble Alpes, CEA, LETI, DTBS
Josef M. Penninger: University of British Columbia
Xavier Gidrol: Univ. Grenoble Alpes, CEA, IRIG/BGE, BIOMICS

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract The development of vascular networks in microfluidic chips is crucial for the long-term culture of three-dimensional cell aggregates such as spheroids, organoids, tumoroids, or tissue explants. Despite rapid advancement in microvascular network systems and organoid technologies, vascularizing organoids-on-chips remains a challenge in tissue engineering. Most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical set-ups. Considering these constraints, we develop a platform to establish and monitor the formation of endothelial networks around mesenchymal and pancreatic islet spheroids, as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 30 days on-chip. We show that these networks establish functional connections with the endothelium-rich spheroids and vascular organoids, as they successfully provide intravascular perfusion to these structures. We find that organoid growth, maturation, and function are enhanced when cultured on-chip using our vascularization method. This microphysiological system represents a viable organ-on-chip model to vascularize diverse biological 3D tissues and sets the stage to establish organoid perfusions using advanced microfluidics.

Date: 2024
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DOI: 10.1038/s41467-024-45710-4

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