Bioengineered Liver Assembloids with Zonation

Abstract

There are a number of pressing issues that the creation of a biomimetic liver culture may be able to solve including catching hepatic mal interactions that are currently missed in preclinical drug screening and offering an alternative solution in the shortage of organs for liver transplant. There are multiple hepatic models that have been created to overcome these issues. However, of the many considerations that need to be taken in the creation of a biomimetic liver model, many fail to capture the functional zone-patterning that is found in vivo. Here is detailed the creation of a hepatic assembloid model that incorporates zone-specific human pluripotent stem cell derived hepatocytes for the recapitulation of zone-patterning in the liver tissues. Use of our lab’s z-wire plate and PGS z-wire scaffold allows for the formation of elongated 3D tissues that resembles the overall morphology of the liver acinus and facilitate the spontaneous development of an aligned vascular-like network. Sustained hepatocyte-specific function in these tissues are promising indicators for application of the hepatic models in drug screening, disease modelling, and regenerative medicine.