Building a Liver From Stem Cells

Reporting in the journal Nature, researchers say they have created a functional liver using induced pluripotent stem cells. The team of scientists first created "liver buds" and transplanted those into mice, where the buds grew into tissue resembling the adult liver. Anthony Atala of the Wake Forest Institute for Regenerative Medicine, who was not affiliated with the work, describes what was done and whether whole, functioning, transplantable organs might be created in this way.

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IRA FLATOW, HOST:

This is SCIENCE FRIDAY. I'm Ira Flatow. Up now, one more step toward the holy grail in stem cell research: growing transplantable human organs in the laboratory. Reporting in the journal Nature, researchers say they have created, in the lab, the first steps toward a functional human liver, and they did this by using stem cells. The scientists created what they called liver buds in the lab, transplanted those into mice, where they say the buds matured into functioning tissue resembling the adult liver. Joining me now to talk more, to comment and analyze the work is Anthony Atala. He's director of the Wake Forest Institute for Regenerative Medicine. He's not one of the researchers who did the work. Welcome back to SCIENCE FRIDAY, Dr. Atala.

DR. ANTHONY ATALA: Good to be with you, Ira.

FLATOW: Tell us a bit more about what the researchers did. What was the - what's the big focus here, the big picture in what they were trying to do?

ATALA: You know, the big picture is that they're using very early cells that can actually differentiate. They can go into different directions in the body, form different types of tissues. And these cells, they show, can actually form these miniature liver structures. You know, it's called a liver bud, and the analogy is that, you know, just like a rose bud give rise to a rose, a liver bud would give rise to a more mature liver tissue. And that's what they did. They actually created these structures in the laboratory.

FLATOW: And were they able to then - are they mature enough, and is the research far enough along that they could then make a real liver? You know, out of those buds.

ATALA: Yeah, well it's early stage at this point, because the structures that were created were just about a fifth of an inch in size. But the hope, of course, is that by using these technologies - these technologies could be advanced in the future to create larger structures that could be used in patients.

FLATOW: And this is just sort of the tip of a large, whole-scale research effort of using different organs, right? To develop all kinds of organs that do things.

ATALA: That's exactly right. I think the field has now seen many different advances in different areas, really tackling all types of tissues and organs, and, you know, of course from the least complex to the most complex. They are different types of organs that get targeted. And there's research ongoing now in pretty much all those tissue types.

FLATOW: I remember we talked about a windpipe that was created and given to a child. Right, that's been shown.

ATALA: That's right.

FLATOW: What else is on our score card here, that are successes and possible successes?

ATALA: Yeah, well, you know, we actually look at this from a perspective of the least complex organs to the most complex, like the least complex being the flat structure, such as skin...

FLATOW: Right.

ATALA: ...you know, that have mostly one cell type. You have tubular structures, like blood vessels, slightly more complex. Then you have hollow, non-tubular organs, like the stomach or the bladder, which are a higher degree of complexity, and finally, the most complex being the solid organs. And up to this point, you know, there are now examples of the very first three types of organs, in terms of flat tubular and hollow non-tubular that have already been placed in patients. And, of course, the holy grail remains the solid organs.

FLATOW: Are there any experiments ready for the solid - big solid organs?

ATALA: Yeah. For the solid organs, basically, there are many different strategies that are being used to really try to attain that. And there's several trials now that are actually targeting solid organs - for example, using cell therapy. Right now, there are technologies where cells are being injected into patients for heart disease. And that's now in progress. And soon, there will also be some trials looking at kidney cells that will be injected into patients with kidney failure. So the technology is definitely advancing for solid organs. And I think it'll be interesting to see what happens over the next few years with the outcomes.

FLATOW: But the experiment that we're talking about with the liver, this was not injecting cells into humans. This was trying to create the beginnings of a real liver in a mouse, in a laboratory.

ATALA: That's correct. This is very early work, of course. But the interesting thing about this work is that it does show that these structures can be really created in a culture dish three-dimensionally by using early stem cells. And the ability to do that really is very interesting, because it allows us to recapitulate how the body develops at an early stage. It allows us to reproduce in a culture dish what the body does in a human, as the human is developing in the womb.

These are very early stage structures that develop usually in the first few weeks of life, at around five or six weeks of life. And that actually give rise to the organ in a human. And now what this work shows is that can also be done in a tissue culture plate.

FLATOW: So is it used as a means of just studying how it develops? Or is the idea to actually create a functioning liver that can be transplanted later?

ATALA: I think both. I think that's the usefulness of this work, is that first it'll allow us to really study how these liver structures do develop in humans over time, and allows us to really look at some of the things that we can do to make that process better, and if there's a disease present. And it also can be used to help us to come up with new strategies that will have us treat patients in the future - in the distant future, of course. We're looking at least, you know, 10 years down the line for any of these technologies to hit patients.

FLATOW: I find it fascinating that a human organ like the liver can actually grow in a mouse.

ATALA: Yeah. You know, it's interesting, because, in fact, the liver regenerates very fast in the human. It's an interesting dichotomy, in fact. Because what happens is if a patient comes into the emergency room and they had a car accident, let's say, and they lost half their liver through the injury and the surgeon just goes in there and resets that injured portion of the liver, if you bring that patient back six months later and you do an x-ray, the liver has fully re-grown. So the liver really does have this great potential to regenerate. The problem, of course, happens when you have a disease in the liver, and that prevents the regeneration from occurring. So having strategies that allow you to help the regeneration process when there's a problem is a good thing.

FLATOW: Is - did these buds actually function in the mice? Were they doing their liver thing?

ATALA: Well, for the most part. They were actually secreting things that the livers secret. They were processing drugs that the liver is supposed to do. But they were not hooking up to the bile, for example, which is part of the liver, which is, you know, a structure that's present within the liver. Or it did not have a rejection response. So these were very immature structures. And - but the strength is that by having these cells created, creating more complex structures, you can actually use these more complex structures for treatment in the future. Instead of just using single-cell suspension - mixtures like what's being today for the heart, for example - you could foresee, in the future, injecting more developed structures into patients.

FLATOW: Isn't there always the chance that if you're using stem cells, that the stem cells might turn into something that you don't want to have, perhaps like a tumor?

ATALA: Well, that's exactly the challenge that is most relevant in this work. And that is that the cells used are what are called induced pluripotent stem cells, or IPS cells, which are basically cells that you get from skin from a patient. We can get those cells from any adult patient. And you can basically get these cells from the skin. And then you're using methods to revert that cell back to a very early stage. But the problem is that when you do that, you're also changing the ability of these cells to be stable. And the cells do become unstable over time. They have the potential to become unstable and form tumors.

FLATOW: With so much - with the aging population and so many people suffering from arthritis and sports injuries, how easy would it be to regenerate cartilage? It seems like that would be one, a one-layer kind of thing, using stem cells.

ATALA: Yes, exactly. Well, cartilage is being used now in patients at limited indications. There are several clinical trials out there now which are looking at cartilage. And right now, you can go to your physician and request treatment with cartilage cells for your knee, as long as there's no arthritis involved. So these technologies are currently available to patients.

FLATOW: All right, I'm headed out the door to my knee doctor. My tennis knee is hurting. Thank you very much, Dr. Atala, for joining us.

ATALA: My pleasure of being with you today.

FLATOW: Have a good weekend. Dr. Anthony Atala is director of the Wake Forest Institute for Regenerative Medicine, and he was joining us from Winston Salem, North Carolina.

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