A method is disclosed wherein human organ cells (e.g. hepatocytes) are cultured in human plasma medium (e.g., 70% to 100% human plasma) in place of the routinely used non-human plasma cell culture growth medium. This culture method allows the human organ cells to be in an environment that closely resembles that of the in vivo environment, where the cells are bathed in human plasma. Also, disclosed herein are cell culture systems containing the human organ cells and human plasma medium in a cell culture vessel. Uses of the cell culture system includes application of cultured human organ cells to evaluate test compound properties, including pharmacological, pharmacokinetic, and toxicological effects of drugs, organ disease progression, such as liver disease progression including hepatitis B infection or hepatitis C infection, or cell biology process, such as gene expression, protein synthesis or response to hormones, that can be directly translated to human in vivo.