Results. After 3 weeks of CDE diet, IL-17/- mice displayed less liver injury as compared to WT mice. IL17-deficiency was associated with reduced CK19+ LPCs, and with weaker induction of LPC activation marker expressions (afoeto-protein, M2-PK, Cx43) when compared with WT mice. In addition, the lack of IL-17 led to a reduction of both macrophage recruitment (F4/80, MCP-1) and pro-inflammatory cytokine expression (TNF-a IL-6) including IL-27. Interestingly, in vitro, IL-17 induced macrophage IL-27 expression. anti-EGFR antibody inhibitor While IL-17 stimulated LPC proliferation, IL-27 treatment led to increased biliary cell (Cx43, CK7, CK19) and hepatocyte (Alb, Cx32, HFN4-a) marker expressions.

Conclusion. Our results revealed that IL-17 directly favors oval cell proliferation, and indirectly enhances their differentiation by inducing macrophage IL-27 production during liver regeneration. Disclosures: The following people have nothing to disclose: Adrien Guillot, Nabila Hamdaoui, Sophie Lotersztajn, Fouad Lafdil Background: A shortcoming of existing transgenic mouse models of cirrhosis is that they only partially recapitulate the features of human liver disease.

Modeling chronic liver disease with human tissue, especially at early stages, may allow for better understanding of the pathophysiology of diseases like non-alcoholic steatohepatitis (NASH). Patient-specific xenograft models may highlight factors driving the variability in disease progression Tideglusib and aid in the selection of therapies that are likely to modify Doxorubicin order disease pathophysiology in particular patients. Methods: Previously, our group and others have used the Fah-/- Rag2-/-Il2ry-/- (FRG) mouse, a model of tyrosinemia, type I, to propagate and study normal human hepatocytes from large surgical wedge resections. Here, 32mm × 16-gauge core needle biopsies were collected from human liver explants or surgically resected tissue with patient consent and intuitional review board approval. No donor tissues were obtained from executed prisoners or other institutionalized persons. Tissue was digested with an

EDTA and collagenase-based digestion protocol in a shaking water bath. Viable hepatocytes were identified by trypan blue exclusion and attachment to tissue culture plates. Hepatocytes were transplanted via the portal vein into FRG mice. Mice were treated postoperatively with antibiotics and cycled on the drug NTBC (nitisinone) to allow selective expansion human hepatocytes. All experimental animal procedures were conducted with the approval and oversight of the OHSU Institutional Animal Care and Use Committee. Results: We show that hepatocytes can be isolated from core needle biopsy tissue of human liver tissue, resulting in liver humanization. Approximately 30,000 – 80,000 live human hepatocytes were isolated per biopsy from diseased liver.