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

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 microvascul...

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Bibliographic Details
Published in:Angiogenesis (London) 2022-11, Vol.25 (4), p.455-470
Main Authors: Bonanini, Flavio, Kurek, Dorota, Previdi, Sara, Nicolas, Arnaud, Hendriks, Delilah, de Ruiter, Sander, Meyer, Marine, Clapés Cabrer, Maria, Dinkelberg, Roelof, García, Silvia Bonilla, Kramer, Bart, Olivier, Thomas, Hu, Huili, López-Iglesias, Carmen, Schavemaker, Frederik, Walinga, Erik, Dutta, Devanjali, Queiroz, Karla, Domansky, Karel, Ronden, Bob, Joore, Jos, Lanz, Henriette L., Peters, Peter J., Trietsch, Sebastiaan J., Clevers, Hans, Vulto, Paul
Format: Article
Language:English
Subjects:
Anastomosis
Angiogenesis
Azathioprine
Biomedical and Life Sciences
Biomedicine
Blood vessels
Cancer Research
Cardiology
Cell Biology
Endothelium
Explants
Grafting
Hepatocytes
Human performance
Liver
Liver transplantation
Microfluidics
Microvasculature
Oncology
Ophthalmology
Organogenesis
Organoids
Original Paper
Spheroids
Tissues
Veno-occlusive disease
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Summary: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.
ISSN:0969-6970
1573-7209
DOI:10.1007/s10456-022-09842-9