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MIT’s new human liver model reveals how it regenerates, giving patients hope to avoid transplants


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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 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 be avoided and help a donated liver grow after being transplanted, according to an MIT news release.

Liver experts told Fox News that the majority of patients who need liver transplants are often those diagnosed with chronic illnesses such as viral hepatitis, primary biliary cholangitis (PBC), cancer or fatty liver disease. The researchers hope that by learning to use the liver’s regenerative properties, clinicians will have more options for treating chronic liver disease.

A view of the Massachusetts Institute of Technology campus on July 8, 2020 in Cambridge, Massachusetts.
(Maddie Meyer/Getty Images)

According to MIT, even if 70% of the liver is removed, the remaining tissue can still grow back to full size within a few months. Meredith Stone is a 50-year-old healthcare professional who was diagnosed with primary biliary cholangitis, an autoimmune disease that attacks the bile ducts in the liver and damages the liver. Stone was not part of the study, but she shared that she now has cirrhosis of the liver, despite not having drank alcohol for more than 20 years. Stone told Fox News that she is currently taking medicines like ocaliva and ursodial in the hope of slowing the progression of the disease and preventing a liver transplant.

“I heard about this study and prayed that these researchers could find a way to help the liver regenerate. It would give me a lot of peace of mind.” Stone added: “There is not much research 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 mouse studies to understand the regeneration pathways that occur after liver injury or disease. According to the report, a key factor is the reciprocal relationship between cells found in the liver called hepatocytes and 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 proliferate. The researchers also said that previous studies in mice found blood flow to be another component in stimulating liver regeneration.

3D illustration of the anatomy of the human body organs (liver)

3D illustration of the anatomy of the human body organs (liver)
(STOCKS)

The MIT researchers wanted to model regenerative interactions in the liver, so they teamed up with Christopher Chen, MD, PhD, the William F. Warren 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 so that molecules such as growth factors can flow between blood vessels and liver spheroids, according to the statement. This design allowed the researchers to remove genes from specific cell types and see how it affects the overall regenerative process.

Sangeeta Bhatia, a member of the Koch Institute for Integrative Cancer Research and the Institute for Medical Science and Engineering at MIT, said in the statement: “For years, people have been identifying different genes that appear to be involved in liver regeneration from mice and some of them seem to be important in humans, but they’ve never figured out all the signals 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. But they found that if they also provided an inflammatory signal, called the cytokine IL-1-beta, liver cells entered the division cycle, according to the release.

The researchers also blocked a gene in endothelial cells that is responsible for producing prostaglandin E2 (PGE2), a molecule that is 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, according to the report.

Liver transplant Surgeons during a liver transplant.

Liver transplant Surgeons during a liver transplant.
(Analogical)

The team plans to explore other growth factors and molecules that are 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 avoid transplant to those patients,” Bhatia said in the MIT statement.

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





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