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Novel hepatocyte culture system enables study of HBV, HCV, malaria
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SAN FRANCISCO — A recently developed culture system could maintain the hepatic phenotype of liver-tropic pathogens such as hepatitis B virus, hepatitis C virus and malaria for longer periods of time than current systems and could aid in evaluating new treatments, according to late breaker data presented at The Liver Meeting 2015.
The novel 3D microfluidic primary hepatocyte culture system is capable of sustaining phenotype for at least 40 days with no alterations to hepatic metabolisms, cell viability or degree of differentiation, the researchers wrote. Cells cultured through this system formed functional microtissues, such as bile canaliculi and tight junctions, and were successful hosts of HBV patient-derived viral isolates and non-JFH1–derived HCV. In addition, malaria sporozoites were able to successfully invade the hepatocytes, “differentiate to merozoites and transition from liver to blood stage,” the investigators wrote.
The researchers also presented proof-of-concept data suggesting the platform’s potential for investigating new treatments. Novel direct-acting antivirals that were demonstrated included Harvoni (ledipasvir/sofosbuvir, Gilead Sciences), for HCV genotypes 1 and 3, and tenofovir alafenamide, for HBV isolates positive and negative for HBeAg.
“The rapid dedifferentiation of primary human hepatocytes in 2D cell culture poses significant limitations to study host-pathogen interactions and to develop novel therapies against these infectious diseases in physiological settings,” the researchers wrote. “This platform offers the unique opportunity to evaluate novel drug candidates targeting HBV cccDNA maintenance as well as the malaria liver stage, dissect host/pathogen interactions in multicellular immune networks as well as serve as a personalized medicine platform for the prediction of treatment outcomes for HCV and HBV.”
Reference:
Ortega-Prieto AM, et al. Abstract LB-7. Presented at: The Liver Meeting; Nov. 13-17, 2015; San Francisco.
Disclosure: Ortega-Prieto reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.