Abstract

Implementing a Scalable Body-on-a-Chip Metabolic Disease Model based on Human Liver and Islet Microtissues

Olivier Frey, Head of Technology and Platforms, InSphero AG

Liver and pancreas constitute key organs in the metabolic syndrome and are highly interacting through different endocrine factors to maintain glucose homeostasis in the human body. An impaired function of one of the organs can cause metabolic diseases, such as diabetes or NASH. Studying these diseases requires a systemic model that can reproduce organ-organ-interactions. The practical implementation of human in-vitro multi-tissue systems in a scalable format includes several challenges. Key aspects encompass biological and technical reproducibility, availability of tissue models, possibility of on-demand production, their usability in suitable treatment windows, access to clinically relevant readouts, and system compatibility with standard lab processes. We implemented a human in-vitro multi-tissue system in a scalable format using 3D organotypic microtissues for establishing organ-organ interactions. The liver model consisted of a primary human hepatocyte/Kupffer cell co-culture with preserved metabolic and inflammatory function over at least two weeks. The primary human islet microtissues comprised all pancreatic endocrine cells at physiological ratio and remained glucose responsive over the same culturing period. The different microtissues were assembled in a microfluidic chip using a pipetting robot enabling an adequate number of replicates at minimal operational complexity for compound testing with access to a wide range of readouts.