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Environmental Factor, September 2015

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Newly discovered cells repair liver without cancer risk

By Virginia Guidry

Hybrid hepatocytes

Hybrid hepatocytes, shown in green, have been shown to regenerate liver tissue following chronic damage. (Photo courtesy of UCSD)

Headshot of Karin

“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. (Photo courtesy of UCSD)

The liver is unique among organs for its ability to regenerate after being damaged. The repair mechanism remained controversial until recently, when researchers funded by NIEHS discovered a type of cell responsible for the process.

The newly discovered cells, known as hybrid hepatocytes, are present in a healthy liver. When liver cells are depleted by chronic damage, such as long-term exposure to toxic chemicals, hybrid hepatocytes multiply rapidly. Importantly, they divide and grow without causing cancer, which is a risk with rapid cell division. The findings were published Aug. 13  in the journal Cell.

“This is the first time anyone has shown how liver cells safely regenerate,” said William Suk, Ph.D., director of the NIEHS Superfund Research Program (SRP).

The wonder of hybrid hepatocytes

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

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

The team studied liver function in mice following chronic exposure to carbon tetrachloride, a chemical commonly associated with Superfund sites. The scientists were able to track the hybrid hepatocytes and observe how they contributed to the regeneration of tissue.

They then exposed healthy mice to three known cancer-inducing pathways and watched the hybrid hepatocytes closely. Liver cancer never originated from any of these cells. The researchers confirmed that there are similar cells in humans.

Potential therapy from cell transplants

There may be therapeutic benefits from this discovery. Chronic liver disease is the main reason for liver transplants.

Hybrid hepatocytes may be an excellent candidate for future cell transplantation, due to their impressive capacity to regenerate tissue without initiating cancer. Moreover, hybrid hepatocytes were unmatched by any other cell in reversing liver damage when transplanted into diseased mice. Their potential depends on how easily the human cells can be isolated and further expanded in culture.

Citation: 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 pepatocytes regenerate the injured liver without giving rise to cancer. Cell 162(4):766-779.

(Virginia Guidry, Ph.D., is a technical writer and public information specialist in the NIEHS Office of Communications and Public Liaison.)

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