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Massachusetts Institute of Technology (MIT)engineers developed a new liver tissue model to help reveal the stages of liver regeneration in hopes of helping those with liver disease† according to a new study published in the journal Proceedings of the National Academy of Sciences. The researchers said that by finding an effective way to stimulate the liver to regenerate itself, some liver transplants could potentially be avoided and it could help a donated liver grow after transplantation, according to a press release from MIT.
Liver experts told Fox News that most patients who need a liver transplant are often those with chronic diseases such as viral hepatitis, primary biliary cholangitis (PBC), cancer or fatty liver. The researchers hope that by learning how to use the liver’s regenerative properties, doctors will have more options to treat chronic liver disease.
According to MIT, even if 70% of the liver is removed, the remaining tissue can still grow back to its full size within months. Meredith Stone is a 50-year-old health care professional who was diagnosed with primary biliary cholangitis, an autoimmune disease that attacks the bile ducts of the liver and damages the liver. Stone was not part of the study, but said she now has cirrhosis of the liver, despite not drinking alcohol for over 20 years. Stone told Fox News she is currently taking medications such as ocaliva and ursodial in hopes of slowing the progression of the disease and avoiding a liver transplant.
“I heard about this study and prayed that these researchers would find a way to help regenerate the liver. It would give such peace of mind.” Stone added: “Not much research is being done on PBC and I just hope they find a way to help my liver regenerate, as well as other people dealing with devastating liver disease.”
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Researchers have used studies of mice to understand the regeneration pathways that occur after liver injury or disease. According to the report, an important factor is the reciprocal relationship between cells in the liver, called hepatocytes, and the cells that line blood vessels, called endothelial cells. The researchers explained that hepatocytes produce factors that help blood vessels develop, and endothelial cells generate growth factors that help hepatocytes multiply. The researchers also said previous studies in mice have shown that blood flow is another part of stimulating liver regeneration.
The MIT researchers wanted to model liver regeneration interactions, so they teamed up with Christopher Chen, MD, PhD, William F. Warren’s distinguished professor of biomedical engineering at Boston University, who designs microfluidic devices with channels that act like blood vessels.
The researchers grew blood vessels along one of these microfluidic channels and then added aggregates derived from liver cells taken from human organ donors.
They developed a chip designed in such a way that molecules such as growth factors can flow between the blood vessels and the liver spheroids, the release said. This design allowed the researchers to turn off genes from specific cell types and see how this affects the overall regenerative process.
Sangeeta Bhatia, who is a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, said in the release: “For years, people have identified several genes that appear to be involved in the regeneration of the liver of mice and some of they seem to be important in humans, but they’ve never been able to figure out all the clues to allow human liver cells to proliferate.”
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This “regeneration-on-a-chip” model showed that increased fluid flow by itself did not stimulate liver cells to divide, which is part of the cycle involved in liver regeneration. But they found that if they also gave an inflammatory signal called the cytokine IL-1 beta, the liver cells entered the division cycle, the release said.
The researchers also blocked a gene in the endothelial cells responsible for making prostaglandin E2 (PGE2), a molecule also involved in liver regeneration in zebrafish. By blocking the gene in these cells, they were able to show that this molecule stimulates human liver cells to enter the cell division cycle, the report said.
The team plans to investigate some other growth factors and molecules produced on their model during liver regeneration. They also hope to find the signals that tell the liver when to stop regenerating.
“Right now, when patients come in with liver failure, you have to transplant them because you don’t know if they’re going to recover on their own. But if we knew who had a strong regenerative response, and if we just stabilize for a while, we can give those patients a transplant,” Bhatia said in the MIT release.
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Bhatia hopes the team of researchers can use molecules to help treat patients with liver failure. The researchers also said another possibility is that doctors may be able to use biomarkers to determine the likelihood of a patient’s liver growing back on its own.