Pump-less, recirculating Organ-on-Chip (rOoC) platform to model the metabolic crosstalk between islets and liver

Aizenshtadt, A. et al. (2024) Pump-less, recirculating Organ-on-Chip (rOoC) platform to model the metabolic crosstalk between islets and liver. Advanced Healthcare Materials, (doi: 10.1002/adhm.202303785) (PMID:38221504) (Early Online Publication)

Abstract

Type 2 diabetes mellitus (T2DM), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD) are epidemiologically correlated disorders with a worldwide growing prevalence. While the mechanisms leading to the onset and development of these conditions are not fully understood, predictive tissue representations for studying the coordinated interactions between central organs that regulate energy metabolism, particularly the liver and pancreatic islets, are needed. Here, a dual pump-less recirculating Organ-on-Chip (dual-rOoC) platform that combines human pluripotent stem cell (sc)-derived sc-liver and sc-islet organoids is presented. The platform reproduces key aspects of the metabolic cross-talk between both organs, including glucose levels and selected hormones, and supports the viability and functionality of both sc-islet and sc-liver organoids while preserving a reduced release of pro-inflammatory cytokines. In a model of metabolic disruption in response to treatment with high lipids and fructose, sc-liver organoids exhibit hallmarks of steatosis and insulin resistance, while sc-islets produce pro-inflammatory cytokines on-chip. Finally, the platform reproduces known effects of anti-diabetic drugs on-chip. Taken together, the platform provides a basis for functional studies of obesity, T2DM, and MASLD on-chip, as well as for testing potential therapeutic interventions.

• Item Type: Articles
• Additional Information: This work received funding from the Research Council of Norway through its Centers of Excellence scheme; project No. 262613, open project support No. 315399, and a Qualification grant No. 329001. Furthermore, financial resources were granted from the South-Eastern Norway Regional Health Authority Innovation project No. 30629 and the European Union’s Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie Actions Grant, agreement No. 801133 (Scientia fellowship), PSC partners and the Norwegian PSC Research Centre.
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gadegaard, Professor Nikolaj and Menezes, Mr Duarte
• Authors: Aizenshtadt, A., Wang, C., Abadpour, S., Menezes, P. D., Wilhelmsen, I., Dalmao-Fernandez, A., Stokowiec, J., Golovin, A., Johnsen, M., Combriat, T. M. D., Røberg-Larsen, H., Gadegaard, N., Scholz, H., Busek, M., and Krauss, S. J.K.
• College/School: College of Science and Engineering > School of Engineering; College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: Advanced Healthcare Materials
• Publisher: Wiley
• ISSN: 2192-2640
• ISSN (Online): 2192-2659
• Published Online: 14 January 2024
• Copyright Holders: Copyright © 2024 John Wiley & Sons Ltd.
• First Published: First published in Advanced Healthcare Materials 2024
• Publisher Policy: Reproduced under a Creative Commons License