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Cited by 1123D Printing in Biomedical ResearchTissue Engineering and Regenerative MedicineMicrofluidic and Capillary Electrophoresis Applications

In vitro grafting of hepatic spheroids and organoids on a microfluidic vascular bed

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Bonanini, Flavio, Kurek, Dorota, Previdi, Sara, Nicolas, Arnaud, Hendriks, Delilah, de Ruiter, Sander, Meyer, Marine, Clapés Cabrer, Maria +18 more·2022·Angiogenesis
DOI 10.1007/s10456-022-09842-9PMC PMC9519670
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Abstract

With recent progress in modeling liver organogenesis and regeneration, the lack of vasculature is becoming the bottleneck in progressing our ability to model human hepatic tissues in vitro. Here, we introduce a platform for routine grafting of liver and other tissues on an in vitro grown microvascular bed. The platform consists of 64 microfluidic chips patterned underneath a 384-well microtiter plate. Each chip allows the formation of a microvascular bed between two main lateral vessels by inducing angiogenesis. Chips consist of an open-top microfluidic chamber, which enables addition of a target tissue by manual or robotic pipetting. Upon grafting a liver microtissue, the microvascular bed undergoes anastomosis, resulting in a stable, perfusable vascular network. Interactions with vasculature were found in spheroids and organoids upon 7 days of co-culture with space of Disse-like architecture in between hepatocytes and endothelium. Veno-occlusive disease was induced by azathioprine exposure, leading to impeded perfusion of the vascularized spheroid. The platform holds the potential to replace animals with an in vitro alternative for routine grafting of spheroids, organoids, or (patient-derived) explants.

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  • Liver-on-chip platforms offer advantages in maintaining hepatocyte function, promoting cell-cell and cell-matrix interactions, and enabling dynamic exposure to drugs and metabolites.

    “Liver-on-chip (LoC) platforms, in particular, offer advantages in maintaining hepatocyte function, promoting cell–cell and cell–matrix interactions, and enabling dynamic exposure to drugs and metabolites in a manner more akin to the intact liver [20, 21].”

    From High-throughput human microfluidic organoid-on-a-chip platform for modeling liver diseases and screening nanotherapeutics. (2026) · cites this paper as [20]

    The Results sections report maintained hepatic function during co-culture, hepatocyte–endothelial contact, ECM deposition, and a perfusable vascular network. They also describe azathioprine exposure, but do not establish dynamic exposure to both drugs and metabolites or show that these interactions more closely reproduce the intact liver. No page numbers are available in our copy. (LLM, conf=0.84)

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References 61 · Cited by 112

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Authors
Bonanini, F., Kurek, D., Previdi, S., Nicolas, A., Hendriks, D., de Ruiter, S., Meyer, M., Clapés Cabrer, M., Dinkelberg, R., García, S. B., Kramer, B., Olivier, T., Hu, H., López-Iglesias, C., Schavemaker, F., Walinga, E., Dutta, D., Queiroz, K., Domansky, K., Ronden, B., Joore, J., Lanz, H. L., Peters, P. J., Trietsch, S. J., Clevers, H., & Vulto, P.
Affiliations
  • Mimetas (Netherlands) (NL)
  • Royal Netherlands Academy of Arts and Sciences (NL)
  • Maastricht University (NL)
Corresponding author
Vulto, Paul
ORCID
Venue
Angiogenesis
Publisher
Springer Science and Business Media LLC
Published
2022-06-15
Volume
25
Issue
4
Pages
455-470
ISSN
  • 0969-6970 (ISSN-L)
  • 1573-7209
DOI
10.1007/s10456-022-09842-9
PMC
PMC9519670
OpenAlex
W4282959276
Cited by
112
References
61
Citations by year
2026: 19 · 2025: 29 · 2024: 38 · 2023: 22 · 2022: 4
FWCI
6.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Angiogenesis (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by)
  • KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders
  • H2020 Innovation In SMEs (848429)
  • Interreg (433)
  • H2020 Marie Skłodowska-Curie Actions (641639, 812616)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
Keywords
liver spheroids, liver organoids, in vitro grafting, microvascular networks, anastomosis, space of Disse, veno-occlusive disease, azathioprine, perfusion, liver regeneration
MeSH terms
Animals, Azathioprine, Humans, Liver, Organoids, Coculture Techniques, Microfluidics

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