Liver organoids for the study of liver biology and disease
Speaker: Meritxell Huch, PhD - Gurdon Institute-Wellcome Trust/ Cancer Research UK, Department of Physiology, Developmental Biology and Neuroscience, University of Cambridge (United Kingdom).
Organizer: IRB Barcelona
Date: Thursday, June 22nd 12.00h
Place: Aula Fèlix Serratosa, Parc Científic de Barcelona, Spain
Host: Dr.Eduard Batlle, IRB Barcelona
Despite the enormous replication potential of the liver, there are currently no culture systems available that sustain hepatocyte replication in vitro. Hepatocytes can be maintained in culture for a few days. However, they lose their hepatocyte phenotype and function almost immediately, thus precluding its application for cell therapy treatments. Liver stem cells have the potential to self-renew and differentiate into functional hepatic lineages. Mouse liver stem cells can be indefinitely expanded in vitro (for >1 year), into "liver organoids", in our liver stem cell culture system, in the absence of a mesenchymal niche. The cultured cells express ductal markers and differentiate into functional hepatocytes in vitro and in vivo. We have now further developed our culture system to study human liver stem cells and human liver disease. We describe a culture system that allows the long-term expansion of adult human liver stem cells (>3 months) from donor biopsies while maintaining their differentiation potential towards functional hepatocytes in vitro. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille Syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine and gene therapy.
Oncology Programme Seminar