Human Hepatocytes

The liver is the largest internal organ in the human body, but more importantly, it is an essential component in metabolism, especially  when we are talking about drugs. Human hepatocytes (the predominant cell type in the liver, which make up 80% of the organ's total mass) are widely used in research.

Ultimately, the cells are used in pharmaceutical research for the study of hepatotoxicity, drug clearance, and drug-drug interactions. They are also widely used in various forms of cell therapy that are aimed at correcting genetic defects, and are used to study treatments for patients with a liver-assist devices.

Although the liver can regenerate in vivo (within the body), this characteristic is lost when the cells are removed from the human body. As a result, it is rather difficult to utilize the cells outside of our skin. Indeed, attempts to proliferate human hepatocytes in laboratories have resulted in cancer cells with little metabolic function.

However, such an issue may have just been addressed by an international team led by The Hebrew University of Jerusalem.

The Breakthrough Approach
Fluorescently labeled polarized Upcyte hepatocytes. Credit: Prof. Yaakov Nahmias

The team of scientists may have just developed a new approach that will allow us to rapidly expand the number of human liver cells in laboratories without losing their unique metabolic function.

The study’s lead author described the breakthrough as the “holy grail of liver research,” in a press release. If implemented, it could allow us to research (and develop treatments for) liver cancer at a fraction of the current cost.

To sum the findings, the researchers showed that weak expression of HPV E6 and E7 proteins released hepatocytes from cell-cycle arrest and allowed them to proliferate in response to Oncostatin M (OSM), which is part of the interleukin 6 (IL-6) superfamily that is involved in liver regeneration.

They were thus able to select colonies of human hepatocytes that only proliferate in response to OSM. If OSM is removed, cell growth is arrested and hepatic differentiation occurs within 4 days, generating highly functional cells.

The team generated hepatocyte lines from ethnically diverse backgrounds that could be serially passaged, while maintaining CYP450 activity, epithelial polarization, and protein expression at the same level as primary human hepatocytes. The proliferating hepatocytes were even demonstrated to have identical toxicology response to primary human hepatocytes across 23 different drugs.

A patent application on the technology has already been submitted.

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