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Research at Mass General
Basak Uygun, PhD, a researcher at the Center of Engineering in Medicine at Massachusetts General Hospital, is devising new ways to build bioengineered livers and liver grafts in the laboratory that could one day be used as an alternative to donor organs.
With the rates of liver diseases such as nonalcoholic fatty liver disease, liver cancer and hepatitis C on the rise, there is a clear need for new treatments for patients with liver failure.
Currently, the only effective treatment is a liver transplant—an imperfect solution due to the shortage of available organs and the side effects of immunosuppressant drugs that transplant recipients take to prevent rejection.
As of July 2017, there were more than 17,000 patients in the United States waiting for a liver transplant, according to the American Liver Foundation (ALF). The long wait time often has fatal consequences—an ALF study estimates that over 29,000 patients died while waiting for a transplant between 1998 and 2013.
One compelling alternative treatment idea is organ bioengineering—essentially growing new organs in the lab that can be used to replace failing ones. It’s a complicated process, but could have a big impact on the outcomes and quality of life for patients with liver failure.
At the Center for Engineering in Medicine at Massachusetts General Hospital, a research team led by Basak Uygun, PhD, is using a blend of engineering and regenerative medicine techniques to bring us closer to achieving this goal.
Making Progress in Stages
In experiments using laboratory models, Uygun has successfully taken a liver that is unsuitable for transplant, removed its existing cells so all that remains is the underlying collagen scaffolding, and repopulated that scaffold with healthy liver cells (typically harvested from another liver).
While the process may seem straightforward, there is still a big gap between putting new cells in the right places and getting the bioengineered organ to function like a human liver.
The liver plays many roles in the body. Its main job is to filter the blood coming out of the digestive tract before passing it to the rest of the body, but it also detoxifies chemicals, metabolizes drugs, makes proteins and blood clotting factors, manufactures triglycerides and cholesterol, and manages glycogen synthesis and bile production.
Creating an organ in the lab that is capable of fulfilling all of those functions is going to take researchers some time.
In the short term, a more attainable goal may be creating smaller grafts of bioengineered liver tissue that can be used as auxiliary transplants for patients who are missing one or two liver functions due to genetic disorders, Uygun says. The grafts could be use replace those missing functions.
If all goes well, researchers may be ready to test bioengineered organ grafts in clinical trials within the next 10 years.
“We’ve shown in principal that it is possible to achieve these steps—you can repopulate a liver scaffold with new cells, you can make it blood-type compatible to some degree, and you can transplant it with a limited amount of survival time," says Uygun. "Right now we are working on different components to make each of these steps better and scaling the process up to human sized livers.”
Claflin Award Provided Timely Support
Uygun was a 2013 winner of a Claflin Distinguished Scholar Award from Mass General. Named after Jane Claflin, a longtime Mass General volunteer and hospital trustee, the awards were established in 1997 to support female investigators balancing the dual demands of career and family.
Uygun says the award came at a crucial time when she was trying to establish an independent research lab. The funds included with the award—$50,000 per year for two years—helped in hiring research staff members to gather confirmatory data for her research.
“Before becoming a mother, I was in the lab 10 hours a day, seven days a week. But that gets completely cut down when you have to be at home with your baby. This type of support is critical, especially if you are working toward independence.”
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