Researchers at Sanford Burnham Prebys discovered stem cell therapy for rare liver disease. They found the new source of stem cells just outside liver that could help cure people with Alagille syndrome. Alagille syndrome is a rare liver disease. It is chronic genetic disorder in which bile ducts of the liver are absent. Hence, leading to acute liver damage and death.
“We’ve been aware of the regenerative power of the liver for a long time, possibly even going back to the ancient Greek myth of Prometheus,” says Duc Dong,Ph.D., an 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.”
Finding new stem cells for liver disease
According to new study, reason these cells were hard to find was that scientist might be looking in the wrong place. Thus, Dong explains that they found stem cells outside the liver not inside which made this discovery difficult. “We think these ‘outside the box’ liver stem cells act more like reserves, only traveling into the liver when all other options are exhausted.” Also, Dong adds, “It only requires a few of these cells to enter the liver and multiply to repopulate all of the cells lost to the disease.”
Almost more than 4000 children are born with Alagille syndrome every year, due to mutation. These mutations stops the duct cells from forming in the liver. This disorder sometimes resolved naturally. Therefore, there are treatment present to control the symptoms. However, it is an incurable disease with 75% death rate without a liver transplant.
“We have known and supported Dr. Dong for years and we feel the work he and his team have done on this disease to date is extraordinary,” says Cher Bork, Executive Director of the Alagille Syndrome Alliance. “Hope can be difficult to come by for families dealing with any incurable disease, and discoveries like this help give that hope back to families living with this life-dominating condition.”
Using animal model
Zebrafish have many same genes and cellular pathways as humans. Thus, it was easy for Dong’s research team to create a model of Alagille syndrome. The model was created by deactivating particular genes related to the syndrome. These genes code for chemical messengers from Notch pathways. “Our work suggests that there is potential for liver regeneration in Alagille patients. But because mutation occurs in signaling pathway, the regenerative cells fail to fully mature into functioning liver duct cells,” says Dong.
In advance animal studies, team showed that the regenerative cells could remobilize to form liver ducts. Accordingly, restoring the function of liver and improving survival. Dong says, “We’ve shown not just that regeneration is possible in models of Alagille syndrome, but, importantly, how it can be enhanced.” Furthermore he adds, “These missing duct cells can regenerate if Notch is restored, and our lab has developed the first drug that can boost this pathway.”
However, to go into clinical trials, the stem cell therapy for rare liver disease require further research. But the team has already found that it can boost regeneration and survival in animal models. Similarly can trigger Notch pathway on cells from Alagille patients. Dong says, “We’re hopeful that this drug will restore the regenerative potential of the liver in Alagille patients, to be more like the liver of Prometheus.”