The current hiPSC-derived models are adapted to reproduce diseases of genetic origin. However, the current two-dimensional HLC (hepatocyte like-cells) model has an immature liver phenotype that is more is closer to a perinatal liver. Furthermore, it does not take into account the complexity of the tissues and the extracellular environment to which the cells are exposed. The development of this type of model could be used to reproduce more pathological conditions such as NASH (Non-Alcoholic SteatoHepatitis) or ASH. In recent years and since the work of Hans Clevers, organoid models have been developed to improve in vitro human study models (Sato et al., 2009), notably with the liver organoid model.
Here, we have chosen to use a hyaluronic acid-based matrix (BIOMIMESYS® Liver) developed by HCS Pharma in which hiPSCs are directly seeded, and where differentiation of the hiPSCs is carried out entirely within this matrix to mimic the different stages of hepatocyte development in 96-well plates. As a result, we observed that many hepatic genes were upregulated and that, in addition to cell organization, different cell types were present within our cell clusters. It was from this point onwards, and after characterizing some of the functionalities of these cell clusters, that we used the term hepatic organoids (LO). Indeed, as we will see later, our liver organoids are composed of different cell types in addition to hepatocytes (stellate cells, cholangiocytes and sinusoidal endothelial cells). They can internalize LDL, and this effect is increased by statins. Also, liver organoids show enhanced CYP activity compared to HLC model.
As ECM is an essential element in health and disease, HCS Pharma develops matrices to mimic the ECM of different organs. If you are interested, feel free to contact us here.