WEDNESDAY, July 3 (HealthDay News) -- Japanese scientists report
they've turned a cocktail of stem cells into the world's first
The tiny livers were created in the lab and transplanted into
mice, where they grew and began to perform the same functions as
human-sized livers, including metabolizing drugs and making
Though very basic -- the experimental livers don't have all the
features of full-grown organs -- it's believed to be the first time
scientists have grown a three-dimensional organ in the lab using
Previously, scientists have made solid organs using stem cells
that are seeded onto some kind of scaffold, either a donor organ
that's been washed of all its original cells or some kind of
But one expert said this latest approach takes the concept one
"This is a different strategy to create tissues and organs," said Dr. Anthony Atala, director of the Wake Forest Institute of Regenerative Medicine, in Winston-Salem, N.C.
"The work is very important because it allows you to study how organs are created and how they give rise to more functional complex systems," Atala said. "This is a nice advance."
With further study, researchers think their technique could one
day solve the critical shortage of human organs for
"We are now assessing the applicability to other organs such as the pancreas and kidneys because they have a similar kind of developmental course as the liver. So far, we've had fascinating results," Takanori Takebe, a professor of regenerative medicine at the Yokohama City University Graduate School of Medicine, said at a press briefing.
Takebe added that he thought it would take at least 10 years
before an organ grown this way could be transplanted into a
For the experiments, described online July 3 in the journal
Nature, researchers mixed three different kinds of stem
cells that each turn into a different kind of tissue.
Pluripotent stem cells -- which have the ability to
differentiate into nearly any type of cell in the body -- were
induced to become liver endoderm, the germ layer that creates the
spongy bulk of liver tissue. Those cells were mixed with
mesenchymal stem cells, which produce connective tissue, and a
population of stem cells derived from human umbilical cord blood
that grow into the tissue that lines blood vessels.
Mixing cell types was important because it mimicked the same
process that happens during fetal development. The different cell
types use chemical signals to talk to each other, orchestrating the
process of organ formation.
"There are no other groups that [I am] aware of that have tried the method described in the paper," Takebe said through a translator.
This is something which other people have kind of overlooked in
their desire to develop and grow pure cell lines, that is the
mixing of stem cells plus other factors that would be required for
the formation of an organ, Takebe said.
After four to six days of growth in a petri dish, the liver
buds, as scientists called them, were transplanted into mice where
they quickly formed new blood vessels that looked like the networks
of arteries and veins in adult livers. The experimental livers
continued to grow for about two months in their mouse hosts.
The vessel growth was an important advance, according to one
"That is a critical step forward, being able to hook it up in the blood vessels so beautifully," said Dr. Mark Donowitz, the Leboff Professor of Medicine at Johns Hopkins University in Baltimore.
Researchers tested them at various stages of development to make
sure they were forming normally. After 10 days, the livers began
producing human liver proteins.
The scientists even challenged the livers with medications like
the painkiller ketoprofen, a drug that humans and mice metabolize
differently. The urine of mice with transplanted liver buds showed
byproducts of human drug metabolism, another sign that livers
maintained their human origins.
In a final experiment, scientists transplanted the new liver
buds into mice with liver failure. The transplanted buds improved
their survival, when compared to mice in liver failure that were
subjected to sham surgeries.
Despite all these promising signs, researchers said they would
continue to be on the lookout for two risks in future experiments
-- cancer and transplant rejection.
In addition to developing into new kinds of organs and tissues,
stem cells can also turn into tumors, a problem that's a constant
worry in the field of regenerative medicine.
And because the organs were grown from cell lines taken from
three different humans, they might be rejected by the immune system
of the eventual host. For that reason, researchers think people who
receive these kinds of lab-grown organs may still need
For more on stem cells, head to the
U.S. National Institutes of Health.
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