The 75th Liver Meeting organized by the American Association for Liver Disease (AASLD) is being held from November 15th to November 19th, 2024 at the San Diego Convention Center.
PhoenixBio is excited to be sponsoring a booth and attending the The Liver Meeting in person in San Diego, California. Meet with our team at Booth #1831 to learn more about PhoenixBio's capabilities and how we can help you advance and deliver tomorrow’s technologies.
While you're here, be sure to attend humanized liver chimeric mouse model related abstracts featured below and grab a chance to speak with our team!
Humanized Liver Related Abstracts:
#3055. Title: Using a Human Liver-On-A-Chip Model To Study Alcohol-Associated Liver Disease By Targeting LSEC and ALDH2
The current experimental approach for studying alcohol-associated liver disease (ALD) has limitations due to insufficient expression and activity of alcohol-metabolizing enzymes in hepatocytes using standard cell culture systems and animal models. Even with a 3D in vitro organoid system, we experience non-physiological structure, inconsistent microenvironment, and uneven nutrient and oxygen supply. Therefore, we developed a Liver-on-a-Chip culture system using human liver cells (PXB-cells), which express relevant levels of alcohol-metabolizing enzymes. There is an unmet need for a human-relevant in vitro 3D culture model to test new therapeutic approaches. In our initial study, we determined that ALDH2 is expressed in liver sinusoidal endothelial cells (LSEC) besides hepatocytes. Intriguingly, senescent LSECs showed reduced expression of ALDH2.
#460. Title: Mathematical Modeling of Acute HBV Infection in Humanized Mice Treated with HBS Antibodies
Background: A novel HBs antibody (Ab) was tested in different doses and at different times post HBV inoculation in humanized mice. We aim to provide insights into the mechanism of action (MOA) of the Ab against HBV dynamics using a mathematical modeling approach.
Methods: Eighteen uPA/SCID humanized mice were inoculated with HBV DNA (6.0 log cp/ml). Serum HBV DNA levels were frequently measured. Of all mice, 3 mice received no Ab, 7 mice received one dose of Ab (33 mpk or 66 mpk) and 8 mice received a second dose of Ab (66 mpk or 100 mpk). First dose was administrated at week 2,4, or 5 and second dose at week 3,5 or 6 post HBV inoculation. We developed multiscale mathematical models and simulated two Ab MOA (i) enhancement of viral clearance from blood, and/or (ii) reduces viral infection. We fixed the natural half-life of HBV (t1/2) in humanized mice at ~60 mins as previously estimated [Hepatology 2018, 68(2): 473-484]. We fit the models with measured data using a population, nonlinear mixed-effects approach. Akaike Information criterion (AIC, lower AIC have better support by the data) was used to identify the best models. Results: Model selection indicates that the main MOA of Ab is to enhance viral clearance (AIC = 363.5) rather than solely reducing viral infection (AIC = 436.3). Modeling suggests HBV t1/2 reduces by 147-fold (~49 sec), 24000-fold (~0.3 sec) and 2400000-fold (~3 msec) after administration of 33 mpk, 66 mpk and 100 mpk, respectively. A negative correlation between the time of administration of Ab and the magnitude of the enhancement in the viral clearance was found. This suggests that the administration of Ab at earlier time points post-infection, which is also associated with the lower levels of viremia, could induce faster clearance. The best model also assumes a waning efficacy at a rate of 0.04- 0.5/day which suggests large variation across mice. Conclusion: Modeling suggests that the main MOA of the novel Ab is enhancing viral clearance in a dosedependent manner.