3D human liver spheroids for translational pharmacology and toxicology.

摘要: Drug development is a failure-prone endeavour, and more than 85% of drugs fail during clinical development, showcasing that current preclinical systems for compound selection are clearly inadequate. Liver toxicity remains major reason safety failures. Furthermore, all efforts to develop pharmacological therapies variety chronic liver diseases, such as non-alcoholic steatohepatitis (NASH) fibrosis, remain unsuccessful. Considering the time expense trials, well substantial burden on patients, new strategies thus paramount importance increase success rates. To this end, human spheroids becoming increasingly utilized they allow preserve patient-specific phenotypes functions multiple weeks in culture. We here review recent application i) predictive mechanistic analyses drug hepatotoxicity, ii) evaluation hepatic disposition metabolite formation low clearance iii) metabolic infectious including NASH, malaria viral hepatitis. envision with increasing dissemination, might become gold standard applications translational pharmacology toxicology.