Turn mice into plants to make human liver cells

Danh Phuong

Researchers at the University of Science and Health have come up with a way to turn a mouse into a plant to get human liver cells, and can be used to check if medications are transferred. how.

Published in Natural Biotechnology, this technique may soon become a gold standard not only to test the metabolism of drugs in the liver, helping scientists identify toxins. of medicine. It is also used as a platform to test new therapies against infectious diseases that attack the liver, such as hepatitis C and malaria.

Medical doctor Markus Grompe, professor of Pediatrics and Department of Medical Genetics and Molecular Medicine at OSHU Medical School, who led the study, said: 'This is very potential if it becomes easy to use. Available and available everywhere, to change how drugs are tested. '

'In the form of research to encourage, this would be great for malaria, hepatitis, liver stem cells, and for gene therapy. It allows many things to happen in rodents that are much simpler to treat and treat. So I'm very happy about this. '

(Photo: Hepfoundation.org.nz) Arundeep S. Pradhan , director of OHSU University's Office of Research and Technology Cooperation, who is responsible for transferring university research findings to the area Trade, said the market demand for Grompe's discovery was very high. OHSU submitted a patent application for technology, and collaborated with Grompe to create a very solid foundation-based company named Yecuris through the university's Springboard Program.

"Yecuris is a viable new company based on significant developments at OHSU," Pradhan said. "Yecuris-developed products have the potential to reduce one of the stalled production processes in drug development: testing drugs for liver toxicity."

According to the business plan for Yecuris, the worldwide market for human hepatocytes that the pharmaceutical industry uses to test the participating drug compounds is estimated at $ 2 billion per year. That's because the liver is an essential place for metabolism of drug mixtures.

Grompe said: "The chemicals are converted into other chemicals in the liver, and you cannot know how the compound you developed in the laboratory will be converted. Usually not. Because drugs have toxins that are the result of metabolism, it is impossible to foresee the transformation of drugs by any existing technology, such as the use of mechanical testing models. For example, you really need to see what human liver cells do to any drug when exposed. '

And human liver cells must be used instead of using laboratory animals because the enzymes in the liver that break down these compounds are special enzymes. He said: ' Animal liver cells treat drugs completely differently than human cells .'

Another obstacle to drug manufacturers is the market for human liver cells that are full of cells that cannot be used or are of poor quality, mostly taken from the liver of survivors. After high quality liver has been saved for transplant needs. In addition, these cells are only available when the samples are available any time of the day or night, and they must be used immediately.

Grompe said: 'There are a number of companies that use these leftover liver, process them and send them to those who need them for testing. When you receive them, you can't control them all. Many waves of cells are delivered very badly, and are of low quality. ' And human liver cells taken from living people are very difficult to develop in tissue culture in the laboratory.

Over the past decade, scientists have been studying whether mice are genetically engineered to develop liver cells in humans. Early results since 2004 show that this is possible, but mice are difficult to keep, the window of time for transplanting human liver cells into mice is very narrow. And rat liver, despite efforts to make animals immune, often reject cells in humans.

Currently, Grompe's lab has a system in which many disadvantages have been removed. It produces a severely immunocompromised mouse, which develops liver disease only when animals do not receive a protective drug called NTBC , allowing liver disease at times.

'The mice we tested on this drug were normal, perfectly healthy mice, and only when we cut off the NTBC supply did they develop liver disease. This is a very simple system that any research lab can install, very different from what is currently available. '

In fact, according to the study, human hepatocytes taken from populations of restorative rat liver cannot be distinguished from normal human liver cells. Grompe said: 'Healthy human liver cells take over and replace diseased rat liver cells. You came to the conclusion that a healthy mouse produces blood-clogging factors. The liver makes all proteins, human bile, everything. '

Mice also retain their unique traits for generations, and each mouse can be implanted with human liver cells at least four times. Grompe estimates that each transplant can produce more than 20 million viable human liver cells.

Grompe said: 'We think we will have true success on this quality and useful cell. We have products. All we need to do is increase and start selling products to anyone who wants to buy it. '

In the coming months, Grompe's lab will develop a library of human liver cells derived from the usual variants of human drug metabolism. Grompe said: 'Different breeds make different metabolites. Therefore, we want to create a library of cells from different human beings to capture somewhat of such variability. '