Without liver transplantation
Scientists have found a way to speed up liver regeneration
Julia Tisler, ERR
The liver is known for its ability to regenerate. It can fully recover even after surgical removal of two-thirds of its mass. But damage from medications, alcohol abuse, or obesity can eventually lead to organ failure. The only effective method of treatment of end-stage liver diseases is transplantation. However, scientists are trying to develop a medicine that could help a severely damaged organ recover on its own.
The problem is that there are not enough organs for transplantation all over the world. In the US, patients have to wait in line for up to five years. Of the more than 11,600 patients on the waiting list for liver transplantation in 2021, only a little more than 9,200 received it. But what if, instead of transplantation, there was a drug that could help the organ recover?
Scientists from the Pittsburgh Research Center, led by Professor Satdarshan Singh Monga, have published a study stating that activating a certain protein with a new drug can help accelerate regeneration and recovery after serious damage or partial surgical removal of the liver in mice.
The liver performs more than 500 key functions in the body, including producing proteins that carry fat through the body, converts excess glucose into glycogen for storage and breaks down toxins, for example, ammonia.
Liver cells, or hepatocytes, perform these tasks using a divide-and-conquer strategy, also called zonality. The organ is "divided" into three zones with different functions, and cells are directed to perform their tasks by turning on certain genes active in each zone. However, what exactly controls the expression of these genes is poorly understood.
Professor Monga and his colleagues identified one group of 19 proteins called Wnt, which play an important role in the distribution of functions and regeneration of the liver. With the help of new molecular mapping technology, scientists have discovered the genes responsible for recovery. Their removal led to a complete stop of liver cell division and, consequently, regeneration.
The discovery made it possible to test a drug that performs functions similar to Wnt proteins. For two days, scientists gave it to mice whose liver cells lacked the genes responsible for regeneration. It turned out that the drug is able to almost completely restore the functions of division and repair of liver cells.
"We also wanted to check how well this drug restored the liver after an overdose of tylenol. Tylenol, or acetaminophen, is an over—the-counter drug commonly used to treat fever and pain. However, an overdose of Tylenol can cause serious liver damage. Without immediate medical attention, this can lead to liver failure and death. Tylenol poisoning is one of the most common causes of severe liver damage requiring transplantation," Monga writes.
It turned out that one dose of the new drug can reduce the number of biomarkers of liver damage — proteins released during damage — in the blood and reduce the volume of dying organ tissues. These results indicate that there is a recovery of liver cells and tissue regeneration.
The study was published in the journal Cell (Hu et al., Single-cell spatial transcriptomics reveals a dynamic control of metabolic zonation and liver regeneration by endothelial cell Wnt2 and Wnt9b).
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