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SUMMARY:Lgr5 liver stem cells and Hepatic organoids - Meritxell Huch\, Gur
 don Institute\, Wellcome Trust/ Cancer Research UK\, Department of Physiol
 ogy\, Developmental Biology and Neuroscience\, University of Cambridge\, U
 K
DTSTART:20150227T143000Z
DTEND:20150227T153000Z
UID:TALK58071@talks.cam.ac.uk
CONTACT:Dr. Monica Vega-Hernandez
DESCRIPTION:Despite the enormous replication potential of the liver\, ther
 e are currently no culture systems available that sustain hepatocyte repli
 cation in vitro. Hepatocytes can be maintained in culture for a few days. 
 However\, they lose their hepatocyte phenotype and function almost immedia
 tely\, thus precluding its application for cell therapy treatments. Liver 
 stem cells have the potential to self-renew and differentiate into functio
 nal hepatic lineages. We have recently described that\, upon liver damage\
 , the intestinal stem cell marker Lgr5 becomes highly expressed in the ste
 m/progenitor cells that contribute to liver regeneration via de-novo gener
 ation of hepatocytes and ductal cells. Mouse liver stem cells can be indef
 initely expanded in vitro (for >1 year)\, into "liver organoids"\, in our 
 novel liver stem cell culture system\, in the absence of a mesenchymal nic
 he. The cultured cells express ductal markers and differentiate into funct
 ional 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 hu
 man liver stem cells (>3 months) from donor biopsies while maintaining the
 ir 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 b
 e converted into functional hepatocytes in vitro and upon transplantation 
 in vivo. Organoids from α1-antitrypsin deficiency and Alagille Syndrome p
 atients mirror the in vivo pathology. Clonal long-term expansion of primar
 y adult liver stem cells opens up experimental avenues for disease modelin
 g\, toxicology studies\, regenerative medicine and gene therapy. 
LOCATION:4th floor Cockcroft building\, New Museums Site\, Pembroke Street
 \, Cambridge CB2 3QG
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