For people suffering from advanced liver disease, the prognosis is bleak. In many patients, such as those with cirrhosis, the liver becomes so clogged with scar tissue that healthy cells are choked off, preventing it from fulfilling its role of filtering toxins. The only cure is a liver transplant. Yet with just 6,000 available organs for some 100,000 patients each year, chances of winning the liver lottery are slim. And if you’re elderly or suffering from another disease, the chances
are closer to zero.
But a surprising new technique under development by University of Pittsburgh stem cell researcher Eric Lagasse may radically improve those odds. Lagasse, based at Pitt’s McGowan Institute for Regenerative Medicine, has discovered how to turn any one of the body’s 500 lymph nodes—the small, oval-shaped organs where immune cells gather to fight invading pathogens—into an incubator that can grow an entirely new liver. Creating a whole set of miniature new livers might take as little as obtaining liver cells from healthy donors and placing them inside the lymph nodes of patients suffering from liver disease.
The concept was born in 2007, while Lagasse was pondering how to overcome a major roadblock to liver regeneration—in those with liver disease, the organ forms scar tissue that destroys its ability to heal. But then he noticed emerging evidence that transplanted liver cells could survive in unusual areas of the body, for instance under the renal capsule, a fibrous layer that protects the kidney from trauma. Lagasse reasoned that if he could implant liver cells away from the diseased organ, instead of succumbing they just might multiply and thrive.
So he set to work trying to grow liver cells outside the dying organ. As his test tube, he used mice with end-stage liver disease, implanting liver cells, or hepatocytes, from another mouse into their kidney capsules, under the skin, and into the spleen. Most of the mice died within eight weeks, the usual prognosis for end-stage liver failure in mice. But that changed when Lagasse injected cells into the belly: The mice gained weight, recovered energy, and within weeks appeared healthy.
After watching those mice thrive for several months, Lagasse repeated the experiment using fluorescent markers to trace the path of the liver cells. To his surprise, they had migrated to lymph nodes, where they grew to form large nodules that, in aggregate, reached a mass capable of keeping the animal alive.
It actually made sense. In many ways, lymph nodes are ideal bioreactors for growing new livers. They have an unusual capacity to expand, allowing them to accommodate an entire organ. They have ready access to the bloodstream, which nurtures new cells with nutrients as well as hormones and signaling agents needed for growth. And since the body has many lymph nodes, some can sacrifice their traditional duties to grow livers. The injections were so successful, Lagasse realized, because the belly provided enough space for cells to migrate.
Further experimentation showed Lagasse that if he injected hepatocytes directly into the lymph nodes, the cells picked up signaling proteins (essentially SOS signals to grow) released into the bloodstream from the dying liver. “There is communication between the new and a diseased liver,” Lagasse says. “They share some functions. We don’t totally understand the signaling mechanism, but we don’t need to if it works.”
Using his technique in mice, Lagasse has already succeeded in growing 20 to 40 small livers that gradually pick up the slack as the central liver fades. Together the mini-livers add up to 70 percent the size of a normal liver.