Newly discovered cells restore liver damage in mice without cancer risk

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The liver is unique among organs in its ability to regenerate after being damaged. Exactly how it repairs itself remained a mystery until recently, when researchers supported by the National Institutes of Health discovered a type of cell in mice essential to the process. The researchers also found similar cells in humans.

When healthy liver cells are depleted by long-term exposure to toxic chemicals, the newly discovered cells, known as hybrid hepatocytes, generate new tissue more efficiently than normal liver cells. Importantly, they divide and grow without causing cancer, which tends to be a risk with rapid cell division.

“This is the first time anyone has shown how liver cells safely regenerate,” said William Suk, Ph.D., director of the Superfund Research Program at the National Institute of Environmental Health Sciences (NIEHS), part of NIH.

The researchers studied liver function in mice following long-term exposure to carbon tetrachloride, a chemical commonly associated with Superfund sites. The scientists were able to isolate the hybrid hepatocytes after observing how the tissue regenerated. They then exposed healthy mice to three known cancer-causing pathways and watched the hybrid hepatocytes closely. Liver cancer never originated from these cells.

The research team, led by Michael Karin, Ph.D., distinguished professor of pharmacology and pathology at the University of California, San Diego (UCSD) School of Medicine and a member of the prestigious National Academy of Medicine, conducted the research at the UCSD Superfund Research Center.

“The entire program at UCSD is focused on the effects of toxicants on liver metabolism and functionality,” said Suk.

One of the goals of the Superfund Research Program is to better understand how toxic chemicals affect human health. The liver plays an essential role in this process by helping to remove toxicants from the body.
“Hybrid hepatocytes represent not only the most effective way to repair a diseased liver, but also the safest way to prevent fatal liver failure by cell transplantation,” noted Karin.

The findings appear Aug. 13 in the journal Cell.

Grant Number: P42ES010337

NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit http://www.niehs.nih.gov. Subscribe to one or more of the href="http://www.niehs.nih.gov/news/releases/newslist/index.cfm">NIEHS news lists

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About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Reference

Font-Burgada J, Shalapour S, Ramaswamy S, Hsueh B, Rossell D, Umemura A, Taniguchi K, Nakagawa H, Valasek MA, Ye L, Kopp JL, Sander M, Carter H, Deisseroth K, Verma IM, Karin M. 2015. Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer. Cell 162(4):766-779.

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