CAMBRIDGE, MA -- More than 10,000 Americans who suffer from chronic liver disease are on a waitlist for a liver transplant, but there are not enough donated organs for all of those patients. Additionally, many people with liver failure aren’t eligible for a transplant if they are not healthy enough to tolerate the surgery.
To help those patients, MIT engineers have developed “mini livers” that could be injected into the body and take over the functions of the failing liver.
In a new study in mice, the researchers showed that these injected liver cells could remain viable in the body for at least two months, and they were able to generate many of the enzymes and other proteins that the liver produces.
“We think of these as satellite livers. If we could deliver these cells into the body, while leaving the sick organ in place, that would provide booster function,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, and a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science (IMES).
Bhatia is the senior author of the new study, which appears today in the journal Cell Biomaterials . MIT postdoc Vardhman Kumar is the paper’s lead author.
Restoring liver function
The human liver plays a role in about 500 essential functions, including regulation of blood clotting, removing bacteria from the bloodstream, and metabolizing drugs. Most of these functions are performed by cells called hepatocytes.
Over the past decade, Bhatia’s lab has been working on ways to restore hepatocyte function without a surgical liver transplant. One possible approach is to embed hepatocytes into a biomaterial such as a hydrogel, but these gels also have to be surgically implanted.
Another option is to inject hepatocytes into the body, which eliminates the need for surgery. In this study, Bhatia’s lab sought to improve on this strategy by providing an engineered niche that could enhance the cells’ survival and facilitate noninvasive monitoring of graft health.
To achieve that, the researchers came up with the idea of injecting cells along with hydrogel microspheres that would help them stay together and form connections with nearby blood vessels. These spheres have special properties that allow them to act like a liquid when they are closely packed together, so they can be injected through a syringe and then regain their solid structure once inside the body.
In recent years, researchers have explored using hydrogel microspheres to promote wound healing, as they help cells to migrate into the spaces between the spheres and build new tissue. In the new study, the MIT team adapted them to help hepatocytes form a stable tissue graft after injection.
“What we did is use this technology to create an engineered niche for cell transplantation,” Kumar says. “If the cells are injected in the absence of these spheres, they would not integrate efficiently with the host, but these microspheres provide the hepatocytes with a niche where they can stay localized and become connected to the host circulation much faster.”
The injected mixture also includes fibroblast cells — supportive cells that help the hepatocytes survive and promote the growth of blood vessels into the tissue.
Working with Nicole Henning, an ultrasound research specialist at the Koch Institute, the researchers developed a way to inject the cell mixture using a syringe guided by ultrasound. After injection, the researchers can also use ultrasound to monitor the long-term stability of the implant.
In this study, the mini livers were injected into the fat tissue in the belly. In the future, similar grafts could be delivered to other sites in the body, such as into the spleen or near the kidneys. As long as they have enough space and access to blood vessels, the injected hepatocytes can function similarly to hepatocytes in the liver.
“For a vast majority of liver disorders, the graft does not need to sit close to the liver,” Kumar says.
An alternative to transplantation
In tests in mice, the researchers injected the mixture of liver cells and microspheres into an area of fatty tissue known as the perigonadal adipose tissue. Once the cells are localized in the body, they form a stable, compact structure. Over time, blood vessels begin to grow into the graft area, helping the injected hepatocytes to stay healthy.
“The new blood vessels formed right next to the hepatocytes, which is why they were able to survive,” Kumar says. “They were able to get the nutrients delivered right to them, they were able to function the way they're supposed to, and they produced the proteins that we expect them to.”
After injection, the cells remained viable and able to secrete specialized proteins into the host circulation for eight weeks, the length of the study. That suggests that the therapy could potentially work as a long-term treatment for liver disease, the researchers say.
“The way we see this technology is it can provide an alternative to surgery, but it can also serve as a bridge to transplantation where these grafts can provide support until a donor organ becomes available,” Kumar says. “And if we think they might need another therapy or more grafts, the barriers to do that are much less with this injectable technology than undergoing another surgery.”
With the current version of this technology, patients would likely need to take immunosuppressive drugs, but the researchers are exploring the possibility of developing “stealthy” hepatocytes that could evade the immune system, or using the hydrogel microspheres to deliver immunosuppressants locally.
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The research was funded by the Koch Institute Support (core) grant from the National Cancer Institute, the National Institutes of Health, the Wellcome Leap HOPE Program, a National Science Foundation Graduate Research Fellowship, and the Howard Hughes Medical Institute.
Cell Biomaterials
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3-Mar-2026