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 Researchers Develop Engineered Tissue That Produces Fully Functional Livers

Researchers at MIT, Rockefeller University and Boston University have developed a new way to engineer liver tissue by organizing tiny sub-units that contain three types of cells embedded into a biodegradable tissue scaffold.
In fact, in a study of mice with damaged livers, the researchers found that after being implanted in the abdomen, the tiny structures expanded 50-fold and were able to perform normal liver tissue functions, according to a post on MIT’s website, news.mit.edu/2017/engineered-liver-tissue-expands-after-transplant-0719.
They say this technology addresses the shortage of livers for transplants that are needed due to diseases such as cirrhosis and hepatitis that can lead to liver failure. With more than 17,000 Americans awaiting liver transplants, this breakthrough is significant.
“There are just not enough organs to go around. Our goal is that one day we could use this technology to increase the number of transplants that are done for patients, which right now is very limited,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, in that same post.
These engineered livers could also help the millions of people who suffer from chronic liver disease, but don’t qualify for a liver transplant, says Bhatia, the senior author of the study, which appeared last summer in Science Translational Medicine.
“These patients never really are transplant candidates, but they suffer from liver disease, and they live with it their whole lives. In that population you could imagine augmenting their liver function with a small engineered liver, which is an idea we’re pretty excited about,” she says.
The new implantable liver builds on previous work by Bhatia’s lab. In 2011 she developed an engineered tissue scaffold, about the size and shape of a contact lens, that could be implanted into the abdomen of a mouse. From there, researchers decided to leverage liver cells’ ability to multiply to generate new liver tissue.
“The liver is one of the only organs that can regenerate, and it’s the mature cells that divide, without an intermediate stem cell. That’s extraordinary,” Bhatia notes.
Working with Christopher Chen, a professor of biomedical engineering at Boston University, Bhatia’s team designed microfabricated structures that incorporate spherical “organoids” made of hepatocytes and fibroblasts, as well as cords of endothelial cells, which are the building blocks of blood vessels. These two types of structures are organized into patterns and embedded into fibrin, a tough protein normally involved in blood clotting.
The idea is simple: to create tiny implantable “seeds” of tissue that produce fully functional livers. And produce they did in the aforementioned study of mice with a genetic liver disorder called tyrosinemia. Bhatia’s team worked with Charles Rice, a virology professor at Rockefeller University, to implant the tissue into mice.
Bhatia explains: “The idea is that it’s the seed of an organ, and you organize it in a way that it can be responsive to these regenerative signals, but it’s a minimal unit of what you eventually want to end up with. What’s really exciting about this is that the architecture of the tissue that emerges looks a lot like the liver architecture in the body.”
As a result of the study, they’re also looking into the possibility of embedding the implant with additional regeneration-promoting chemicals that they discovered in 2013.
The researchers are also exploring the best source of cells for these implants. They’re currently using liver cells from human organs that can’t be transplanted because they were on ice too long after being removed from the donor or had some unusual anatomy.
Other possibilities include using liver cells taken from the patient who will be receiving the tissue, which would avoid the need for immunosuppressive drugs, or using liver cells generated from induced pluripotent stem cells.
The National Institutes of Health, the Howard Hughes Medical Institute, the Skolkovo Institute of Science and Technology, and the National Institute of Environmental Health Sciences funded the research. The paper’s lead author is Kelly Stevens, a former Koch Institute postdoc.
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