ena-STUDY-NIOB-28-05-2014-13:16:43:833-492
Human liver stem cells remain genetically stable during long term in vitro expansion and allow disease modeling
Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. ES and iPS cells have emerged as an alternative source of hepatocytes. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of single adult human liver stem cells. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. In vitro, the cells can readily be converted into functional hepatocytes. Organoids from a1-antitrypsin deficiency patients mirror the in vivo pathology. In conclusion, clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine and gene therapy.
Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. ES and iPS cells have emerged as an alternative source of hepatocytes. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of single adult human liver stem cells. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. In vitro, the cells can readily be converted into functional hepatocytes. Organoids from a1-antitrypsin deficiency patients mirror the in vivo pathology. In conclusion, clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine and gene therapy.