Lab technician using microscope.
(photo credit: INGIMAGE / ASAP)
A living “library” of highly functional human liver cells has been grown in the lab by an international research group headed by a Hebrew University of Jerusalem team. This achievement could advance a variety of discoveries and applications – from studying drug toxicity to creating bio-artificial liver support for patients awaiting transplants.
“This is the holy grail of liver research,” said Prof. Yaakov Nahmias, the study’s lead author and director of HU’s Alexander Grass Center for Bioengineering. He partnered with prominent German scientists at upcyte technologies GmbH (formerly Medicyte) to develop a new approach to rapidly expand the number of human liver cells in the laboratory without losing their unique metabolic function.
“Our technology will enable thousands of laboratories to study fatty liver disease, viral hepatitis, drug toxicity and liver cancer at a fraction of the current cost.” Nahmias noted that genetic modifications preclude using the hepatocytes for transplantation, “but we may have found the perfect cell source for the bio-artificial liver project.”
The liver cells represent varying genetic backgrounds for scientific, clinical and pharmaceutical development.
Called by liver experts a “breakthrough,” the new research appears in the latest issue of the prestigious journal Nature Biotechnology.
The liver is the largest internal organ in the human body, serving as the main site of metabolism. Human hepatocytes – cells that comprise 85% of the liver – are routinely used by the pharmaceutical industry for study of hepatotoxicity, drug clearance and drug-drug interactions. They also have clinical applications in cell therapy to correct genetic defects, reverse cirrhosis, or support patients with a liver-assist device.
Unfortunately, while the human liver can rapidly regenerate in living tissue – as recognized by the ancient Greeks in the myth of Prometheus – this capability to proliferate is rapidly lost when human cells are removed from the body. Thus far, attempts to expand human hepatocytes in the laboratory resulted in immortalized cancer cells with little metabolic function. The scarce supply of human hepatocytes and this inability to expand them without losing function is a major bottleneck for scientific, clinical and pharmaceutical development.
The method, described as the “upcyte process,” allows expanding human hepatocytes, resulting in a quadrillion cells from each liver isolation, compared to only a billion cells that can be isolated from a healthy organ. “The approach is revolutionary,” said Dr. Joris Braspenning, who led the German group. “Its strength lies in our ability to generate liver cells from multiple donors, enabling the study of patientto- patient variability and idiosyncratic toxicity.”
The proliferating hepatocyte library was recently commercialized by upcyte technologies GmbH in Hamburg; Yissum, HU’s R&D company, and the German company submitted a joint patent application earlier this year and are actively seeking investment.