Functional Human Liver Cells Grown in the Lab

In November Nature Biotechnology published an article called “Long-term culture and expansion of primary human hepatocytes”. We asked one of the authors, Dr. Yaakov Nahmias from The Hebrew University of Jerusalem, to comment on this study.

The Study

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We found that poor expression of Human Papilloma Virus (HPV) proteins released hepatocytes from cell-cycle arrest and permitted them to multiply as a result of exposure to Oncostatin M – an immune cytokine recently found to be involved in liver regeneration.

While previous efforts caused hepatocytes to multiply without control, converting hepatocytes into tumor cells with little metabolic ability, we carefully picked colonies of human hepatocytes that only multiply in response to OSM. Activation with OSM triggered cell growth with a doubling time of 40 hours. Removal of OSM caused growth to stop, allowing the cells to regain a high level of metabolic activity within 4 days. We created a library of various genotypes of functional liver cells that can be used for drug discovery and toxicity screening.

Background

We have always been fascinated by the limitless capacity of the human liver to regenerate its cells from even massive trauma, thought to be recognized by the ancient Greeks in the myth of Prometheus. However, this capacity to proliferate is lost when cells are removed from the body.

Initial work in mouse and rat cells showed promise, but didn’t translate to human hepatocytes. It was clear that the cells were locked in a dormant state. We sought to find a key that can wake this dormant potential to regenerate in the lab.

Future directions

Our technology will enable laboratories across the world to study fatty liver disease, viral hepatitis, drug toxicity and liver cancer at a fraction of the current cost. While the genetic modifications preclude using the cells for transplantation, this might be an ideal cell mass for the bio-artificial liver project.