The present disclosure provides a culture medium formulation comprising human serum that can enhance functions of primary human hepatocytes, improve morphology, promote bile canaliculi formation and extend hepatocyte functional lifetime in vitro for over 10 weeks as compared to ˜3-4 weeks when using a conventional culture medium containing serum from bovine sources. The provided long-term culture model can be used to screen drugs for their efficacious and/or toxic effects over several weeks, improve drug-transporter assays via the larger bile canaliculi network, and to model several chronic liver diseases such as hepatitis, type 2 diabetes, malaria, liver fibrosis, liver cancer, and fatty liver disease.
