Chronic liver injury is a feature of several hepatic diseases that remains poorly treated. In steatohepatitis, dysfunction of the non-parenchymal cellular interactive network in the response to lipotoxic insults can lead to hepatocyte loss. Here, a fully defined hydrogel is used to develop a suitable microenvironment that supports pluripotent stem cell-derived hepatocytes and non-parenchymal-like cells to investigate liver steatosis, inflammation and fibrosis caused by steatohepatitis. The results show that this 3D culture setup reproduced pathological features of diverse hepatic diseases better than the correspondent monocultures of the different cell types present in the model. Overall, the researchers propose a new 3D hydrogel-based co-culture system that could potentially be used to elucidate the underlying mechanisms of liver steatosis, inflammation and fibrosis and to design therapeutical strategies to rescue or protect against them.
A fully defined matrix to support a pluripotent stem cell derived multi-cell-liver steatohepatitis and fibrosis model
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