If you did not attend this year’s annual AASLD’s Liver Meeting® in San Francisco (CA), you may be interested in the most recent presentations relevant to chimeric mice with humanized liver, and human hepatocytes, isolated from these mice.
Both oral presentations were focused on hepatitis B application of humanized liver mouse model. Benitec Biopharma explored non-viral CELiD (Closed-Ended Linear Duplex) DNA vectors expressing anti-HBV shRNAs as a promising therapeutic for chronic HBV infection. University of Tokyo researchers tried to find an inhibitor for HBV regulatory protein X (HBx) interaction with the host DNA damage-binding protein 1.
3 out of 10 poster presentations, featuring PXB-Mouse® and PXB-cells®, received AASLD’s Presidential Poster of Distinction, which speaks for the quality of the research projects of PhoenixBio Group and their colleagues at various organizations.
Liver Fibrogenesis session showcased presentation on screening of pharmaceuticals for preventing liver fibrosis using PXB-mice by Niigata University in collaboration with Towa Pharmaceuticals (abstract 1121). Five leads were screened using chimeric mice with humanized liver, and the most promising candidate was selected based on the expression of genes, related to liver fibrosis, in human liver tissues. One of the drug candidates resulted in a significant decrease in the expression of genes related to liver fibrosis progression (including CTGF). This compound was later studied with mouse liver fibrosis model. It is interesting, that utilizing mice with humanized liver for preliminary may have reduced the overall number of mice used, which aligns with 3Rs approach within PhoenixBio Group (check our 3Rs article for more details).
Another fibrogenesis related abstract (#2001) from academic group in Japan utilized PXB-cells® to investigate the roles of TTL1 in hepatic fibrogenesis and carcinogenesis.
Pediatric hepatology session abstract (#1848) was presented by PhoenixBio R&D department. The presentation shared company’s recent development of a human Ornithine Transcabamylase Deficiency (OTCD) model using proprietary PXB-Mouse®, transplanted with OTCD patients’ hepatocytes.
One of the AASLD’s Presidential Poster of Distinction was the one with the novel Jak3KORagKO chimeric mouse model (abstract 1006). Mice were successfully infected with hepatitis C (HCV) and hepatitis B (HBV), and they are useful for the study of hepatitis virology and the evaluation of antiviral agents for hepatitis viruses.
Another Presidential Poster of Distinction utilized PXB-cells® for HBV research (#528). Host molecules involved in HBV life cycle were investigated by genome-wide siRNA-based screening in human hepatocytes (PXB-cells®).
“Liver fibrosis induced by gut microbes in chimeric mice model with human hepatocytes persistently infected with hepatitis B virus” is one more Presidential Distinction poster (#529). The data suggest that liver fibrosis (F1-2) seen six months post-infection, could occur by certain types of bacteria in the gut-live axis.
The rest four abstracts were in viral hepatitis sessions and were focused on promising therapies for curing hepatitis B, and the potential treatment of HCV drug resistance-associated variants using PXB-mice.
It is not surprising that chimeric mouse model with humanized liver has an important place in liver-related research. It continues to be one of the most relevant tools in studies of human-specific mechanisms in drugs and chemicals development.
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PXB-Mouse® is the registered trademark for proprietary cDNA-uPA/scid chimeric mouse model with highly humanized liver. PXB-cells® is the registered trademark for ~95% pure human hepatocytes isolated from PXB-Mouse®.