BACKGROUND: Hepatic cell therapy has become a viable alternative to liver transplantation for life-threatening @entity409 . However, the supply of @entity1 hepatocytes is limited due to the shortage of suitable donor organs required to isolate high-quality cells. @entity1 pluripotent stem cells reflect a potential renewable source for generating functional hepatocytes. However, most differentiation protocols use undefined matrices or factors of animal origin; as such, the resulting hepatocytes are not Good Manufacturing Practice compliant. Moreover, the preclinical studies employed to assess safety and function of @entity1 embryonic stem cell (hESC)-derived hepatocytes are generally limited to immunodeficient @entity19 . In the present study, we evaluate the generation of hepatocytes under defined conditions using a European hESC line (VAL9) which was derived under animal-free conditions. The function capacity of VAL9-derived hepatocytes was assessed by transplantation into @entity19 with @entity1443 -induced @entity879 , a clinically relevant model. METHODS: We developed a protocol that successfully differentiates hESCs into bipotent hepatic progenitors under defined conditions, without the use of chromatin modifiers such as @entity3733 . These progenitors can be cryopreserved and are able to generate both committed precursors of @entity4837 . RESULTS: Thirty days post-differentiation, hESCs expressed hepatocyte-specific markers such as asialoglycoprotein receptor and hepatic nuclear factors including @entity16525 . The cells exhibited properties of mature hepatocytes such as @entity1133 secretion and @entity14014 and cytochrome P450 activities. When transplanted into @entity19 with @entity1443 -induced @entity879 , a model of @entity409 , the VAL9-derived hepatocytes efficiently engrafted and proliferated, repopulating up to 10  % of the liver. In these transplanted livers, we observed a significant decrease of liver transaminases and found no evidence of tumourigenicity. Thus, VAL9-derived hepatocytes were able to rescue hepatic function in @entity1443 -treated animals. CONCLUSIONS: Our study reveals an efficient protocol for differentiating VAL9 hESCs to neonatal hepatocytes which are then able to repopulate livers in vivo without @entity5 induction. The @entity1 hepatocytes are able to rescue liver function in @entity19 with @entity1443 -induced acute @entity137 . These results provide proof-of-concept that replacement therapies using hESC-derived hepatocytes are effective for treating @entity409 .

Transplantation of hESC-derived hepatocytes protects XXXX from liver injury.

@entity1 :: ('9606', 'Species') :: ['human', 'Human'] @entity16525 :: ('15378(Tax:10090)', 'Gene') :: ['HNF4a'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity4837 :: ('MESH:D007567', 'Disease') :: ['cholangiocytes and neonate-like hepatocytes'] @entity1133 :: ('MESH:D014508', 'Chemical') :: ['urea'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity879 :: ('MESH:D017114', 'Disease') :: ['acute liver failure'] @entity14014 :: ('394436(Tax:10090)', 'Gene') :: ['UGT1A1'] @entity409 :: ('MESH:D008107', 'Disease') :: ['liver diseases', 'liver damage'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumour'] @entity3733 :: ('MESH:D004121', 'Chemical') :: ['dimethyl sulphoxide'] @entity1443 :: ('MESH:D000082', 'Chemical') :: ['acetaminophen']
@entity19 :: (10090,Species) :: ['mice']
