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 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.


PubMed ID: 35704148

Projects: PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Publication type: Journal

Journal: Angiogenesis

Citation: Angiogenesis. 2022 Nov;25(4):455-470. doi: 10.1007/s10456-022-09842-9. Epub 2022 Jun 15.

Date Published: 16th Jun 2022

Registered Mode: by PubMed ID

Authors: F. Bonanini, D. Kurek, S. Previdi, A. Nicolas, D. Hendriks, S. de Ruiter, M. Meyer, M. Clapes Cabrer, R. Dinkelberg, S. B. Garcia, B. Kramer, T. Olivier, H. Hu, C. Lopez-Iglesias, F. Schavemaker, E. Walinga, D. Dutta, K. Queiroz, K. Domansky, B. Ronden, J. Joore, H. L. Lanz, P. J. Peters, S. J. Trietsch, H. Clevers, P. Vulto

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Created: 20th Sep 2023 at 15:13

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