New Stem Cell Identified By Sanford Burnham Prebys Researchers Offers Hope To Patients With Rare Liver Disease

Newswise – LA JOLLA, CALIF. – October 11 – Sanford Burnham Prebys researchers have discovered a new source of stem cells just outside the liver that could help treat people with Alagille syndrome, a rare, incurable genetic disorder in which the bile ducts of the liver are missing , resulting in severe liver damage and death. The results, recently published in the journal Hepatology, have broad biomedical implications for Alagille syndrome and for liver disease in general, including cancer.

“We have been aware of the regenerative power of the liver for a long time, perhaps even dating back to the ancient Greek myth of Prometheus,” says lead author Duc Dong, Ph.D., associate professor in the human genetics program. at Sanford Burnham Prebys. “But the existence and nature of liver stem cells remains an intensely debated topic.”

The new study suggests that the reason these cells were so hard to find may be that the researchers looked in the wrong place.

“The stem cells that we found are actually outside the liver, not inside, which may have made it difficult to find them,” Dong adds. “We believe these ‘off the beaten path’ liver stem cells act more like stores, only traveling to the liver when all other options are exhausted. It only takes a few of these cells to enter the liver and multiply to repopulate all the cells lost to the disease.

Each year, more than 4,000 babies are born with Alagille syndrome, which is caused by a mutation that prevents the formation of duct cells in the liver. And although the syndrome can sometimes resolve itself naturally and treatments are available to manage the symptoms, the disease is incurable, leading to a 75% death rate in late adolescence for people without a liver transplant.

“We have known and supported Dr Dong for years and believe that the work he and his team have done to date on this disease is extraordinary,” said Cher Bork, Executive Director of the Alagille Syndrome Alliance. “Hope can be hard to find for families struggling with an incurable disease, and findings like this help bring that hope back to families living with this life-dominating disease.”

Using zebrafish, which has many of the same genes and cell pathways as humans, Dong’s research team were able to create a model of Alagille syndrome by selectively turning off genes associated with Alagille syndrome. These genes code for chemical messengers of the Notch pathway, a signaling system found in most animals and involved in embryonic development and maintenance of adult cells.

“Our work suggests that there is potential for liver regeneration in Alagille patients, but because this signaling pathway is mutated, regenerative cells fail to fully mature into functional hepatic duct cells,” says Dong.

In other animal studies, the team showed that by genetically restoring this signaling pathway, regenerative cells could remobilize to form hepatic channels, restoring liver function and improving survival. The researchers are now using their discovery to develop new therapies for Alagille syndrome.

“We have shown not only that regeneration is possible in models of Alagille syndrome, but, more importantly, how it can be improved,” said Dong. “These missing channel cells can regenerate if Jagged / Notch is restored, and our lab has developed the first drug that can stimulate this pathway.”

While the new drug requires further studies to move on to clinical trials, the team has already found that it could improve regeneration and survival in animal models and can trigger the Notch pathway in cells from Alagille patients. These results will be published in separate studies.

“We hope this drug will restore the potential for regeneration of the liver in Alagille patients, to look more like Prometheus’ liver,” Dong adds.


About the Sanford Burnham Prebys Medical Research Institute

Sanford Burnham Prebys is an independent and preeminent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to have a profound impact on human health. For more than 40 years, our research has produced breakthroughs in cancer, neuroscience, immunology and childhood illnesses, and is supported by our NCI Designated Cancer Center and advanced discovery capabilities of medications. For more information, visit us on or on Facebook and on Twitter@SBPdiscovery.

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