Stem Cell Advance: The Little Liver That Builds Itself

"Liver buds" grow in a petri dish. The proto-organs are about 5 mm wide, or half the height of a classic Lego block. (Courtesy of Takanori Takebe/Yokohama City University Graduate School of Medicine via NPR)

“Liver buds” grow in a petri dish. The proto-organs are about 5 mm wide, or half the height of a classic Lego block. (Courtesy of Takanori Takebe/Yokohama City University Graduate School of Medicine via NPR)

The journal Nature reports today that Japanese scientists used human stem cells to create “liver buds” — tiny precursors to full-fledged livers — that were then implanted into mice and functioned much like regular livers.

In other words, it appears that we’ve come our closest yet to actually building a solid-tissue human organ from stem cells. It will likely be a decade or more until this advance might help the many patients waiting desperately for transplants, but for now, stem cell experts say this is a significant breakthrough in regenerative medicine.

See the full NPR report on the experiment here, and the New York Times here. I spoke a bit earlier about the Nature report with Here & Now host Jeremy Hobson. Our conversation:

JH: So first of all, what did the researchers do here?

Well, what they did not do is use those politically controversial embryonic stem cells. These were what’s called “induced pluripotent stem cells,” they’re adult cells that have been kind of “reprogrammed” to be able to develop into various cell types.

What the researchers did was to mix together three types of human stem cells, and they found — to their own surprise, the first time they observed it — that the cells self-organized, or self-assembled, into a three-dimensional liver bud. A liver bud is normally found in an early embryo, and it later develops into a full-fledged liver.

But this experiment didn’t produce a full-fledged liver, did it?

That’s right, no, it didn’t. It produced kind of a teeny tiny proto-liver. It’s what scientists call an organoid, a structure like an organ.
The researchers transplanted the human liver buds into mice to see how they’d function, but not into their liver areas — the buds were put into the mouse’s abdomen or inside the head, just to see how they’d do. But those results were encouraging: The buds matured and developed blood vessels, and they produced proteins, which is a normal liver function. They also seemed to be able to save mice from liver failure.

How big a step is this, and were we able to do anything similar before?

This seems to serve as ‘proof of concept’ that a liver can be built…I spoke with Chad Cowan, an assistant professor at the Harvard Stem Cell Institute who was not involved with this research, and he says this was a first in stem cell science. He says it’s the closest we’ve come to a real solid-tissue organ that’s been engineered or created.

So when can humans take advantage of this?

In terms of helping human patients, we’re definitely not there yet. For instance, in this case, it’s not simple to get from this teeny functioning precursor of a liver to a real liver. By the way, livers are big — the average human liver weighs about three pounds.

Chad Cowan of the Harvard Stem cell Institute says: “The researchers very honestly say this is ten years in the future. While the concept or the way it might occur could be the same, it’s going to have to be done at a scale that’s say, ten thousand times larger just to make something that’s even close to one human liver.”

And that’s not a trivial challenge, to scale up like that.

So where do researchers go from here? Can this technique be used with other organs?

If this technique works on livers, it’s possible it will also work on other organs — kidneys, lungs, the Japanese researchers are already working on a pancreas. This kind of self-assembly has already been used on a retina, part of the eye.

Scientists say it’s hard to believe it could be this easy to build an organ — I mean, imagine if you wanted to build a building and all you had to do was put the right construction materials on the site, and they’d build themselves. But life is full of surprises — and by life, I mean life science, biology — so these self-assembling stem cells will certainly be an area to watch…

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  • PLB

    Livers already regenerate if there’s some left like after resection, when there’s only 30% left, it will regrow within months. Seems to me that makes it easier for liver creation than other organs.

  • Maureen

    My husband’s only hope for eyesight is with stem cell research. I’ll take any positive news on stem cell research.

  • focker

    everything is ten years in the future…

    • good_idea

      Right.
      You wonder if it’s real, or just a play to get more funding.