A hepatocyte, a human liver cell, stained red and green. (Courtesy of Lagasse Laboratory/McGowan Institute of Regenerative Medicine)

Liver Failing? Grow Some New Ones

A startup’s wild idea for creating organ factories in the body.

You might have to read this twice for it to sink in.

Instead of giving people liver transplants, doctors could inject liver cells into their lymph nodes so that auxiliary livers grow there.

Strange as it might sound, it appears to work in mice, where the surrogate mini-livers made up for the missing function of a diseased liver. Tests in pigs have been encouraging, too, and now trials in humans could begin late in 2018 if Eric Lagasse and Michael Hufford can raise about $10 million for their startup, LyGenesis.

“I think there’s a real beauty and simplicity to this approach,” says Hufford, who is LyGenesis’s CEO.

Lagasse, a stem cell researcher at the University of Pittsburgh, came up with the idea over a decade ago in hopes of saving lives. In the United States alone, tens of thousands of people are diagnosed annually with a very serious liver problem, such as hepatitis or fatty liver disease, that prevents their bodies from properly filtering toxins. A liver transplant is generally their only option. But only around 8,000 liver transplants are performed every year, primarily because of the difficulty of acquiring organs from donors.

The ideal solution would somehow tap directly into the liver’s remarkable capacity for regeneration — the organ can grow back even after two-thirds of it is removed. Indeed, other researchers are testing methods of repairing livers by coaxing healthy cells to grow in place of diseased ones.

Lagasse questions how well such techniques can work in end-stage liver disease, when the organ is so scarred that it’s not very hospitable to new cells. It’s an “environment that is destroyed,” he says. But Lagasse noticed in experiments in mice that injected liver cells often survived just fine elsewhere in the body, away from the scarred liver. And they did especially well in lymph nodes.

You have about 600 lymph nodes in your body. They’re a key part of the immune system because they churn out T-cells. Lagasse’s idea is to hijack as few as three to six lymph nodes and use them as hospitable places for liver cells to reproduce.

In an outpatient procedure that would be far less invasive than a liver transplant, liver cells from a donor would be injected in lymph nodes in the patient’s abdomen, in connective tissue called the mesentery that shares blood vessels with the liver. In time, these lymph nodes would transform into mini-livers and perform their usual function of filtering the blood.

Experiments in mice and pigs indicate that these auxiliary livers can buy time for the original liver to repair itself or for a full transplant to become available— in which case, the lymph node livers shrink and eventually disappear. Incredibly, the body apparently will maintain no more liver than it needs for healthy function. It’s also intriguing that the lymph node-hijacking method might also work with thymus cells (which play a role in the immune system), kidney cells, and pancreatic cells that produce insulin.

Several big questions still need to be answered in human trials, which LyGenesis hopes to launch late next year under a Food and Drug Administration program that accelerates testing of regenerative technologies. Mini-livers grown in lymph nodes won’t necessarily perform as hoped. Joe Zhou, a stem cell researcher at Harvard, said he was unfamiliar with Lagasse’s research but would be curious to see whether the auxiliary livers could grow large enough and have the right structure and links to the circulatory system to be effective.

And although advances in cell engineering could someday mean that a patient’s own cells could be injected into the lymph nodes, for now cells from a donor would still be required — along with immune-suppressing drugs that transplant recipients have to swallow to stave off organ rejection.

Lagasse and Hufford acknowledge the uncertainties but are optimistic they’re onto something big. Transplanting cells rather than entire livers would mean that one organ donor could supply 75 to 150 patients rather than just one. That would dramatically alter the grim math for people on the transplant waiting list.

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