Hassan Rashidi
University of Edinburgh, UK
Posters & Accepted Abstracts: J Cancer Sci Ther
Development of in vitro model to accurately predict in vivo drug toxicity is one of the greatest challenges of the pharmaceutical industry today. Freshly isolated human adult hepatocytes are considered to be the gold standard tool to evaluate human drug metabolism and safety in vitro. However, primary hepatocyte scarcity, cell cycle arrest and the rapid loss of liver-phenotype post isolation are major limitations. Immortalized and hepatoma cell lines have therefore been employed as potential alternatives, however, their poor functionality, karyotypic instability and higher tolerance to toxicological insult limit their widespread application. Human embryonic and induced pluripotent stem cells provide renewable resources to obtain hepatocyte-like cells (HLCs) in vitro. Although HLCs can be derived efficiently from pluripotent stem cells under conventional monolayer protocols, they exhibit foetal features and have a transient phenotype which limits their applications. We have successfully developed a protocol to derive functional HLCs under three- dimensional (3D) condition. Unlike their 2D counterpart, the 3D HLCs exhibit mature and stable phenotype for over 200 days in vitro. More importantly, the cells remained metabolically active and drug-inducible during the culture period providing a better in vitro platform to evaluate long-term effect of new lead compounds in more physiologically relevant setup.
Email: hrashidi@exseed.ed.ac.uk
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