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

Flavio Bonanini, Dorota Kurek, Sara Previdi, Arnaud Nicolas, Delilah Hendriks, Sander de Ruiter, Marine Meyer, Maria Clapés Cabrer, Roelof Dinkelberg, Silvia Bonilla García, Bart Kramer, Thomas Olivier, Huili Hu, Carmen López-Iglesias, Frederik Schavemaker, Erik Walinga, Devanjali Dutta, Karla Queiroz, Karel Domansky, Bob RondenJos Joore, Henriette L Lanz, Peter J Peters, Sebastiaan J Trietsch, Hans Clevers, Paul Vulto

Research output: Contribution to journal/periodicalArticleScientificpeer-review

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)455-470
Number of pages16
JournalAngiogenesis
Volume25
Issue number4
DOIs
Publication statusPublished - Nov 2022

Keywords

  • Animals
  • Azathioprine
  • Coculture Techniques
  • Humans
  • Liver
  • Microfluidics/methods
  • Organoids

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