A Chemically Defined Hydrogel for Human Liver Organoid Culture

Here, a novel hydrogel-based on polyisocyanopeptides (PIC) and Biolaminin-111 is described for human liver organoid cultures. PIC is a synthetic polymer that can form a hydrogel with thermosensitive properties, making it easy to handle and very attractive for clinical applications. PIC hydrogel alone was not sufficient to support organoid growth. The addition of a laminin-entactin complex (LEC) to the plain PIC gel, resulted in efficient organoid formation and proliferation that seemed comparable to the Matrigel controls, with lower stiffnesses most favorable for organoid proliferation. The stem cell phenotype and proliferation and differentiation capacity of the organoids could be maintained in PIC-LEC over several passages, enabling their seemingly unlimited expansion and subsequent maturation. Moreover, organoids can be efficiently differentiated toward a hepatocyte-like phenotype with key liver functions. Importantly, they also show that the LEC in the PIC-LEC gels could be replaced by Biolaminin-111, resulting in a completely synthetic hydrogel for the expansion of human liver organoids.