Scientists Grow A Simple, Human Liver In A Petri Dish

Jul 3, 2013
Originally published on July 4, 2013 9:48 am

Japanese scientists have cracked open a freaky new chapter in the sci-fi-meets-stem-cells era. A group in Yokohama reported it has grown a primitive liver in a petri dish using a person's skin cells.

The organ isn't complete. It's missing a few parts. And it will be years --maybe decades — before the technique reaches clinics.

Still, this rudimentary liver is the first complex, functioning organ to be grown in the lab from human, skin-derived stem cells. When the scientists transplanted the organ into a mouse, it worked a lot like a regular human liver.

"It's a huge step forward," George Daley, from the Harvard Stem Cell Institute, tells NPR's Rob Stein.

"There have been groups that have attempted to generate liver cells, and that's been promising," says Daley, who wasn't involved in the current study. "This is the first attempt to regenerate the organ by mixing the cells that are critical components of that organ."

Several labs around the world have been trying to grow organs on plastic scaffolds, which offer a three-dimensional surface on which cells can stick.

This approach has been used to make tracheas from a person's own cells. And doctors have even transplanted these synthetic organs into a handful of patients.

But more complex organs – kidneys, pancreases and livers – have been elusive. So Takanori Takebe and a team at the Yokohama City University tried a more laid-back strategy: They let the cells build their own scaffold.

The team took some liver cells (made from a person's induced pluripotent stem cells) and then mixed them with two other cell types — one that makes blood vessels and one that builds connective tissue to hold an organ together.

Five days later, Takebe was "completely gobsmacked," by what he saw in the petri dish, he told reporters Tuesday, with the help of a translator.

The cell mixtures had assembled into tiny 3-D structures that looked and acted like miniature livers, or "liver buds," as Takebe calls them.

The proto-organs were only about 5 millimeters tall, or half the height of a Lego brick. But the liverettes built their own blood vessels, which allowed Takebe and his team to test-drive them in mice.

They plucked the liver buds from the petri dish and then connected them to blood vessels in a mouse. About 10 days later, the buds started working. They broke down human drugs and made blood proteins, as a regular liver would.

One proto-organ even saved a mouse from liver failure, Takebe and his colleagues report in the journal Nature.

The results are "extremely encouraging," says stem-cell scientist Stuart Forbes, from the University of Edinburgh. "But there's a significant amount of further research [required] before we could translate this to a clinical therapy for patient," he tells Stein.

First off, the organs are too small to be useful. Doctors would need thousands of them to help a person with liver damage. And the little buds don't form a full liver. They're missing bile ducts, or the tubes that drain away toxins.

Plus, Forbes says, there's still a big question about safety. Stem cells tend to form tumors. And the current study doesn't look at the long-term effect of the transplanted liver. "To perform this in humans, we'd like to see a lot of safety testing," Forbes says.

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We're learning this morning about an event that's being hailed as a milestone in medicine. Scientists in Japan have created human livers in a laboratory. This marks the first time researchers have created a complex organ using stem cells. Here's more from NPR's Rob Stein.

ROB STEIN, BYLINE: Ever since scientists discovered stem cells, the ultimate goal has been to use them to make tissues, and even whole organs to treat diseases. Harvard stem cell researcher George Daley says scientists have made some progress.

GEORGE DALEY: There have been groups that have attempted to generate liver cells, and that's been promising. There's been other groups that have seeded scaffolds, like from a donor trachea with cells, and created a trachea, which is kind of like an organ.

STEIN: But no one had been able to make a whole organ, or anything really close, until now. In this week's issue of the journal Nature, researchers at the Yokohoma City University in Japan report they have produced structures that are similar to primitive human livers. The researchers described their work during an international telephone briefing.

UNIDENTIFIED WOMAN: First, we're going to hear from the lead author of the paper, Professor Takenori Takebe.

TAKENORI TAKEBE: OK, so, with this study, we succeeded in generating the human liver precursor. We call this liver buds.

STEIN: Liver buds, because they're very tiny, and they don't have all the parts a regular liver has. But when Takebe's team transplanted them into mice, they did the most important things livers do. They attached themselves to blood vessels. They produced key proteins. They broke down chemicals in the animals' blood. And they can even keep the animals alive after their own livers had failed.

TAKEBE: Taken together, we concluded that this liver is functioning.

STEIN: So how did they succeed, where so many others failed? They mixed together three types of cells: stem cells known as induced pluripotent stem cells, umbilical cord cells and cells from bone marrow. Interpreter Matthew Salter stepped in during the briefing to help Takebe explain what happened next.

MATTHEW SALTER: They noticed that during that process, that some of the plates they were using had allowed them to grow these three-dimensional structures. As a result of that, they realized this extraordinary result, which gave them a functioning, three-dimensional liver bud.

STEIN: At first, Takebe and his colleagues couldn't quite believe what they had done.

SALTER: It's a little difficult to translate directly, but he was completely, I think gobsmacked is probably the word in English, absolutely surprised and thought, you know, this is something which he really couldn't predict.

STEIN: But after confirming his results with other researchers, Takebe was convinced, and other experts are hailing the results. Stephen Forbes is a liver specialist who's been doing similar research at the University of Edinburgh.

STEPHEN FORBES: Well, it's very exciting.

STEIN: Forbes says laboratory-made livers could someday help thousands of patients suffering from liver failure.

FORBES: Given that there's insufficient donor livers available for transplantation, that would be a very exciting future use.

STEIN: Now, everyone agrees that much more work is needed before the stem cell livers will be ready to help any patients. For one thing, the liver buds the Japanese scientists created don't have bile ducts, which are needed to drain away toxins, and according to Harvard's George Daley, so far, they're too small to keep a human alive.

DALEY: This is very early. It's a very different matter to make enough liver buds to save a mouse. The scale-up alone for treating a human is a Promethean task. But this is the first step.

STEIN: Takebe predicts it will take 10 years before anyone is ready to start testing his stem cell livers in humans. But he has already started to use the same approach to try to make other organs, including kidneys and pancreases. And so far, that work looks promising, too. Rob Stein, NPR News. Transcript provided by NPR, Copyright NPR.