iPS-derived ‘mini liver’ offers hope for treatment of liver diseases

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A research group has succeeded in developing “miniature livers,” or organoids, through using induced pluripotent stem (iPS) cells, which will greatly assist researchers in developing treatments for liver diseases.

The team, headed by a professor of Tokyo Medical and Dental University (TMDU), created organoids that replicate livers as they develop into an inflammatory condition marking the first time that such “organs” were made from iPS cells.

The finding was published in the online Cell Metabolism journal on May 30.

“By creating ‘miniature organs’ from iPS cells, it is possible to reproduce the state of difficult diseases,” said Takanori Takebe, professor at the Institute of Research, Division of Advanced Research of TMDU, who headed the research team. “It is likely a technique that can be applicable to diseases of the lungs or intestines in the future.”

The researchers developed a reproducible method to derive multicellular human liver organoids composed of hepatocyte-, stellate-, and Kupffer-like cells, in which inflammation can develop, leading eventually to non-alcoholic steatohepatitis (NASH), a fatty liver disease.

NASH can be developed even though a patient does not drink alcohol. Recently, the number of such cases has increased, and millions of people are thought to be suffering from NASH in Japan.

If the disease progresses, it can lead to cirrhosis or liver cancer. Very little is known about how NASH develops and there is no effective treatment.

The team developed an artificial liver, measuring 0.2 millimeters in diameter, which shows the state of fat accumulating in the liver, similar to what is occurring in a human body.

The researchers placed fatty acid into a miniature liver and it accumulated as fat, making the organ hard, which is the same condition as seen in cirrhosis.

After a certain chemical compound was placed onto the liver, fat was prevented from accumulating. Thus, researchers can seek an effective treatment for NASH through trial and error with livers created from iPS cells.

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