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Massachusetts Institute of Technology (MIT)engineers have developed a new model of liver tissue to help reveal the stages of liver regeneration to help people with liver disease., According to a new study published in the journal Proceedings of the National Academy of Sciences. By finding an effective way to stimulate the liver’s own regeneration, researchers say it may be possible to avoid some liver transplants and help the donor liver grow after transplantation, according to an MIT media release.
Liver specialists told the News that most patients who need liver transplants are usually those with chronic diseases such as Fox virus hepatitis, primary biliary cholangitis (PBC), cancer or fatty liver disease. Researchers hope that by learning how to harness the liver’s regenerative properties, doctors will have more options for treating chronic liver disease.
According to MIT, even if 70% of the liver is removed, the remaining tissue can grow back to full size within months. Meredith Stone is a 50-year-old healthcare professional who was diagnosed with primary biliary cholangitis, an autoimmune disease that attacks the liver’s bile ducts and damages the liver. Stone, who was not involved in the study, said he now has cirrhosis of the liver, despite not drinking alcohol for more than 20 years. Stone told Fox News that he is currently taking drugs such as Ocaliva and Ursodial to slow the progression of the disease and prevent a liver transplant.
“I heard about this study and prayed that these researchers could find a way to regenerate the liver. It would give me a piece of mind.” Stone added, “There is a lot of research going on with PBC, and I hope they find a way to help my liver and other people struggling with devastating liver diseases.”
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Researchers have used studies in mice to understand the recovery pathways that occur after liver injury or disease. According to the report, one of the key factors is the interaction between cells in the liver called hepatocytes and cells that line the blood vessels called endothelial cells. The researchers explained that hepatocytes produce factors that help blood vessels develop, and endothelial cells produce growth factors that help hepatocytes multiply. The researchers also found that previous studies in mice showed that blood flow is another factor that stimulates liver regeneration.
The MIT researchers wanted to model the interaction of liver regeneration, so they designed microfluidic devices with channels that function like blood vessels, Boston University Distinguished Professor of Biomedical Engineering William F. Warren is joined by Christopher Chen, MD, PhD.
The researchers grew blood vessels along one of these microfluidic channels and then added aggregates from liver cells taken from human organ donors.
They developed a chip designed to allow molecules such as growth factors to flow between blood vessels and liver spheroids, according to the release. This project allowed researchers to delete genes in specific cell types and see how it affects the overall recovery process.
Sangeeta Bhatia, a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science, said: “For years, people have identified various genes that appear to be involved in mouse liver regeneration, and some of them seem to be important in humans, but they have never been found in human livers.” They could not understand all the signals to multiply their cells.
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This “regeneration-on-a-chip” model showed that increased fluid flow alone did not stimulate liver cell division, which is part of the cycle involved in liver regeneration. But they also found that liver cells enter a cycle of division when they give off an inflammatory signal called a cytokine called IL-1-beta.
The researchers also blocked the gene responsible for making the prostaglandin E2 (PGE2) molecule in endothelial cells, which is also involved in zebrafish liver regeneration. 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 team plans to study the growth factors and molecules produced in their model during liver regeneration. They also hope to find signals that tell the liver when to stop regenerating.
“Currently, 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 know who has a regenerative response, and if we just need to stabilize them for a while, we can save those patients from a transplant,” he said. Bhatia said in a statement from MIT.
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Bhatia’s research team hopes to be able to use the molecules to help treat patients with liver failure. The investigators also said that another possibility is that doctors could use biomarkers to determine whether a patient’s liver is likely to regrow on its own.