Poster – A single procedure to generate functional hiPSCs-derived liver organoids -Towards an innovative tool suitable for drug screening

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We previously showed that human pluripotent stem cells (hiPSCs) provide a suitable model to study metabolic diseases upon hepatocyte-like cell (HLC) differentiation. In particular, HLCs have been used to model cholesterol metabolism regulation, by mimicking the main disease features in vitro. Human iPSCs can be generated from urine samples of patients with a well-described phenotype and carrying specific genotypes. This non-invasive approach allowed the study of LDLR- and PCSK9-mediated autosomal dominant hypercholesterolemia (ADH) as well as PCSK9-mediated familial hypobetalipoproteinemia (FHBL). While the direct link between hiPSCs and patients, as well as the abundance of HLCs provide promising advantages of such strategy, it is impaired mainly by the neonatal characteristic of HLCs as well as the difficulty to perform high throughput studies for pharmacological investigations.

Therefore, to overcome these burdens, we choose to :
1. Differentiate hiPSCs into HLCs in a 3D environment to enhance their maturation;
2. Adapt our 3D differentiation process to a 96 wells format to make it compatible for drug
screening.