Engineering the liver

The liver is a critical and intriguing organ, and our understanding of it continues to evolve to this day. As reported in a paper published earlier this week in Proceedings of the National Academy of Sciences, Broad and MIT researchers teamed up to put artificial liver tissue to the test (read the news story here and Project Spotlight here). This tissue, engineered in the lab from frozen human cells, can be implanted in mice where it reproduces drug interactions, drug metabolism, and drug-induced liver injuries usually seen only in humans.

In honor of this vital organ, we’ve put together five fast facts about what’s known – and what remains mysterious – about the liver.

Hundreds of functions. In addition to breaking down drugs, the liver helps metabolize proteins, carbohydrates, and fats found in food. It also breaks down important hormones like insulin and builds essential components such as amino acids. Since the liver plays such a critical role in so many basic processes, liver failure can have widespread complications. Scientists in Sangeeta Bhatia’s lab at MIT have been working for many years to create artificial liver tissue in part to help predict what drugs may cause the liver harm.

Vital but vulnerable. The liver is an important defensive mechanism – it can break down potential toxins ingested in food. But the liver is also vulnerable, both to chemicals and to pathogens. Some infectious diseases, such as hepatitis B and C, target the liver. Drugs, such as acetaminophen, can also cause liver failure when taken at too large a dose. The Bhatia lab estimates that each year 40,000 people in the United States die from liver failure and 2 million people may die worldwide. Their goal is to engineer tissue that will help them study the fate and function of liver cells.

Drug safety. Since the liver breaks down drugs, scientists pay careful attention to it when testing drugs for safety and efficacy. Broad researchers identified 83 enzymes in the human liver that play an important role in breaking down most drugs. They tested the expression of these enzymes in the artificial tissue to see how well it modeled normal human liver tissue.

Regeneration. In Greek mythology, the titan Prometheus suffers a horrible punishment: every day, an eagle eats his liver, and every night the organ grows back. The myth may have a kernel of truth to it: the liver does have the remarkable ability to regenerate itself. Researchers have studied the intricate interplay of molecules that direct this regrowth, but it remains unclear exactly how this process is triggered.

Beyond drug toxicity. The new study from MIT and the Broad focuses on predicting potentially toxic drugs, but artificial liver tissue and the analytical tools for looking at liver enzymes can be used for other purposes as well. The researchers’ goals include not only identifying harmful drugs that could lead to liver disease, but also developing therapies to help treat patients at risk of liver disease.