MIT’s new human liver model shows how it regenerates and gives patients hope to avoid transplants

Massachusetts Institute of Technology (MIT)Engineers have developed a new liver tissue model to reveal the stages of liver regeneration in hopes of helping people 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 the transplant, according to an MIT media release.

Liver experts told Fox News that most of the patients who need a liver transplant are often those who have been diagnosed with chronic diseases such as viral hepatitis, primary biliary cholangitis (PBC), cancer or fatty liver. Researchers hope doctors will have more options for treating chronic liver disease by learning how to harness the liver’s regenerative properties.

Even if 70% of the liver is removed, the remaining tissue can grow back to its full size within months, according to MIT. 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 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 that she is currently taking medications like Ocaliva and Ursodia in hopes of slowing the disease’s progression and preventing a liver transplant.

“I heard about this study and prayed that these researchers could find a way to help the liver regenerate. Stone added, “There isn’t much research being done on PBC and I just hope they find a way to help my liver regenerate, as do other people struggling with devastating liver disease.”

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Researchers have used studies in mice to understand the regenerative pathways that occur after liver injury or disease. According to the report, a key factor is the mutual relationship between cells found in the liver called hepatocytes and the cells lining blood vessels called endothelial cells. The researchers explained that hepatocytes produce factors that help blood vessel development, and endothelial cells produce growth factors that help hepatocytes proliferate. The researchers also said that previous studies in mice found that blood flow is another component in stimulating liver regeneration.

The MIT researchers wanted to model liver regeneration interactions, so they teamed up with Christopher Chen, MD, PhD, the William F. Warren Distinguished Professor of Biomedical Engineering at Boston University, who is developing microfluidic devices with channels that act like blood vessels.

The researchers grew blood vessels along one of these microfluidic channels, then added aggregates derived 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, the release said. This design allowed the researchers to turn off genes from specific cell types and see how this affects the overall regeneration process.

Sangeeta Bhatia, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute of Medical Technology and Science, said in the press release, “For years people have identified various genes that appear to be involved in liver regeneration in mice, and some of them appear to be to be important in humans, but they never managed to find all the clues that make human liver cells proliferate.”

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This “regeneration-on-a-chip” model showed that increased fluid flow alone did not stimulate liver cells to start dividing, which is part of the cycle involved in liver regeneration. However, they found that the liver cells entered the cycle of division when they were also delivering an inflammatory signal called the cytokine IL-1-beta, the press release said.

The researchers also blocked a gene in the endothelial cells responsible for the production of prostaglandin E2 (PGE2), a molecule also involved in liver regeneration in zebrafish. According to the report, 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 some other growth factors and molecules produced in 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 robust regenerative response and if we just needed to stabilize them for a while, we could spare those patients a transplant,” Bhatia said in the MIT release.

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Bhatia hopes the research team can use molecules to treat patients with liver failure. The researchers also said another possibility is that doctors could potentially use biomarkers to determine the likelihood of a patient’s liver regrowing on its own.