Building a Liver From Stem Cells

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.
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
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
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
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: 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
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.