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Work Package One: hIPSC-derived immunocompetent models of liver, intestine and white adipose tissue

We will develop immunocompetent models of liver, intestinal epithelium and white adipose tissue. Our aim is to create 3D organotypic models containing key tissue-specific cells supported by stroma vascular cells and interspersed with immune cells.

Work Package Two: Microfluidic chip design and establishing ‘healthy microtissues’

We have pioneered engineering microfluidic devices for complex multiorgan tissue models that allow recreating dynamic in-vivo like behaviours of microtissue models for enhanced functional representations. In this project we will design microfluidic bioreactors to host the immunocompetent liver, gut, and adipose microtissue models to provide them with biomimetic in-vivo like microvascular flows with improved oxygen and nutrient transport as well as physiological fluidic shear stresses that are key to long-term maintenance of their viability and functions.

Work Package Three: Disease modelling and model validation using clinical data and tissue samples

MASLD is a highly complex multisystem disease, involving cross talk between different organs to drive liver and systemic effects and adverse clinical outcomes. This cross-talk between organs is not recapitulated incurrent human in-vitro models, whilst no murine model adequately reflects the spectrum of changes that occur in humans. In this WP, we will utilise our dynamic immunocompetent gut-liver-adipose tissue model to study the impact of organ cross-talk, dysbiosis and host factors (e.g. genetic background, ethnicity) on liver injury and fibrosis.

We will determine the optimal combination of tissue injury and cross-talk between organs to recapitulate patient liver injury and fibrosis.