Scientists have identified a new stem cell situated just outside the liver.

Scientists have discovered a new stem cell.

Scientists have discovered a new stem cell in a unique microenvironment known as a niche just outside the liver. The team also used these cells to regenerate organ function lost to a rare condition called Alagille syndrome. The findings, published in the journal Hepatologyhave resounding implications for liver disease, including cancer.

Your liver is a vital filtering system that removes waste from the body using bile ducts. It does this by forming a substance known as bile which then mixes with harmful toxins to channel them through these conduits to the small intestine. If you do not have enough of these ducts, poisonous waste accumulates, causing damage to the hepatic tissues and possible organ failure.

Alagille syndrome is passed on from parent to child via a mutation in the JAGGED1 gene. This genetic marker is part of the notch signaling system that helps regulate many different organs in the body – with any disruption causing a malfunction. In this case, the condition leads to the loss of bile duct cells and decreased bile flow, hampering the liver’s ability to rid the body of toxins. As the disease can sometimes resolve itself in patients, researchers posit that spontaneous regeneration of these ducts has occurred. However, the mechanism of this phenomenon is unclear with many sufferers needing a liver transplant.

An alternative may now be on the horizon, thanks to researchers from Sanford Burnham Prebys, who have identified a new source of stem cells just outside the liver. The team also used the cells to regenerate bile ducts – holding massive implications for rare diseases affecting this organ.

The researchers used zebrafish with the same mutation found in patients with Alagille syndrome; these fish also presented with a loss of hepatic bile ducts. The newly discovered stem cells were observed migrating to the liver and regenerating the cells that make up these ducts. However, this event only occurs when the disrupted notch signaling system increases naturally.

The lab simulated this natural phenomenon using a novel drug to restore the signaling pathway artificially. The system used the extraneous stem cells to regenerate the bile ducts as it would in nature to restore organ function and improve animal survival rates. The team now plans to use their discovery to develop therapies to treat liver disease.

“We’ve shown not just that regeneration is possible in models of Alagille syndrome, but, importantly, how it can be enhanced,” says Dong. “These missing duct cells can regenerate if Jagged/Notch is restored, and our lab has developed the first drug that can boost this pathway.” 

He stresses that although their drug shows great promise in animal models, where it enhances bile duct regeneration, further investigation is needed to advance it to clinical trials.

Source: Sanford Burnham Prebys

Image courtesy of @pch-vector on freepik

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