29 November

Using liver organoids to study liver disease

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Researchers from the Hubrecht Institute in Utrecht, the Netherlands, and Rockefeller University in New York, USA, have developed a method by which they can grow liver cells into mini-livers in the lab. These mini-livers can be used to study viral infections of the liver (such as hepatitis B and C) and hereditary liver diseases. These mini-livers might replace laboratory animals in studies on possible adverse effects of new drugs and may complement current approaches to liver transplantation. The researchers publish their results in the scientific journal Cell today.

Liver disease
The liver is a chemical factory with a variety of functions, such as the removal of toxins and drugs from the blood, the production of bile for the digestion of fats and the storage of energy in the form of glucose. When the liver is damaged due to a toxin, a virus infection or hereditary disease, its ability to perform these functions decreases. The search for treatment of these diseases is hampered by the lack of a proper laboratory model for the human liver. At the moment, researchers have to use laboratory animals or cells derived from ‘rejected’ transplant-livers. Such human cells can only survive in the lab for a few days. Using this newly developed model, one can learn more about the human liver in health and disease and study the (adverse) effects of drugs more carefully.

Mini livers…
The researchers have developed a method by which liver cells derived from mice or humans can be grown in the lab as ‘liver organoids’ for many months. Because these mini-livers are produced from liver cells, or hepatocytes, they closely resemble the real liver. The cultured human mini-livers are functional when they are transplanted into mice with a hereditary liver disease.

… may lead to new treatment
Virus infections in the liver, such as hepatitis B or C, increase the chance of liver cancer. Ongoing research shows that these diseases can be studied in the cultured mini-livers. In addition, these mini-livers can also be produced using liver cells derived from patients with hereditary liver disease. This could bring possible treatment of these diseases within reach.

Replacing laboratory animals
The possible harmful effects of new drugs are investigated in toxicological studies. Currently, this research depends heavily on laboratory animals. In collaboration with Stichting Proefdiervrij, a Dutch foundation aimed at eliminating the use of laboratory animals, we have started a study to test the human mini-liver technology as a replacement for toxicological research in laboratory animals.

Long-term expansion of functional mouse and human hepatocytes as 3D organoids. Huili Hu, Helmuth Gehart, Benedetta Artegiani, Carmen Lopez-Iglesias, Florijn Dekkers, Onur Basak, Johan van Es, Susana M. Chuva de Sousa Lopes, Harry Begthel, Jeroen Korving, Maaike van den Born, Chenhui Zou, Corrine Quirk, Luis Chiriboga, Charles M. Rice, Stephanie Ma, Anne Rios, Peter J. Peters, Ype P. de Jong, Hans Clevers. Cell 2018

Prof. dr. Hans Clevers is group leader at the Hubrecht Institute, professor of Molecular Genetics at the University Medical Center Utrecht and Utrecht University and Oncode Investigator.

Dr. Ype de Jong is assistant professor in Gastroenterologiy and Weill Cornell and guest investigator at The Rockefeller University, both in New York.