New Stem-Cell Source Could Alter Debate
Stem cells derived from amniotic fluid show great promise in the lab and may end the divisive ethical debate once and for all.
By Mary Carmichael
Updated: 10:01 a.m. PT Jan 7, 2007
Jan. 7, 2007 - Stem-cell research is divided into two major camps: one focused on cells from adults, the other on the controversial technique that destroys embryos. But important research published Sunday supports the idea of a third way, a new category of stem cells that are readily available, perhaps ethically trouble-free and possibly as powerful and flexible in function as their embryonic counterparts: "amniotic-fluid stem cells," found in both the placenta and the liquid that surrounds growing fetuses.
The cells are "neither embryonic nor
adult. They're somewhere in between," says Dr. Anthony Atala, a
tissue-engineering specialist at
All of that means the cells come with little "ethical baggage," says David Prentice, a senior fellow in life sciences at the Family Research Council, which has a longstanding position against embryonic-stem-cell research. "I'm just pumped up by this," adds Prentice. "It's fantastic."
The AFS cells thrive and divide in the amniotic fluid and placenta throughout the gestation process. Scientists have studied them for several years, but the new research is the first to fully characterize them and demonstrate their potential. "What Dr. Atala has done is to present eloquently, for the first time, the real power that these cells have," says Dr. Roger De Filippo, a urologist and tissue engineer at Childrens Hospital Los Angeles who called the research a "sentinel paper."
Like those from embryos, the AFS cells are pluripotent, or able to transform into fully-grown cells representing each of the three major kinds of tissue found in the body. Using stem cells taken by amniocentesis from 19 pregnant women, Atala and his colleagues were able to create in the lab nerve cells, liver cells, endothelial cells (which line blood vessels) and cells involved in the creation of bone, muscle and fat. (De Filippo's lab has also coaxed amniotic cells into becoming structures found in the kidneys.) Some of the cells in Atala's lab even functioned as they would be expected to in the human body. The liver cells secreted urea, an activity otherwise seen exclusively in their natural counterparts. And, in a development that may hearten patients with Parkinson's disease and other neurological disorders, the lab's nerve cells secreted glutamate—a neurotransmitter that is crucial to memory and helps to form dopamine, which Parkinson's patients lack. The lab also conducted tests on mice with a neurodegenerative disease and showed that the amniotic cells sought out and repopulated damaged areas of the brain.
Amniotic-fluid stem cells share another unique characteristic with embryonic stem cells: they multiply quickly and are remarkably long-lived. The Atala lab's cells divided more than 250 times—more than quintuple the life expectancy for stem cells taken from adults. Dr. Dario Fauza, a surgeon at Children's Hospital Boston, says he had achieved comparable results working with stem cells from amniotic fluid: "I practically haven't been able to get them to stop growing." The cells are hardy, a trait that makes them relatively easy to culture. "If you think about where they are in nature, they're floating in the amniotic fluid, in which there is very little oxygen," says Fauza. "So they are very tolerant to low oxygen levels, which makes it easier to manipulate them in the lab."
That resilience may eventually help doctors trying to grow new organs or graft tissue into patients. "When you implant an engineered graft, it's typically vulnerable early on, because it takes a few days for the host to send blood vessels to feed it," says Fauza. "So you need a cell that can take that punishment for a while." You also need, says De Filippo, "a lot of cells to create organs"—a demand that the amniotic cells may meet even more easily than embryonic cells can. In addition, for reasons that are still poorly understood, the amniotic cells do not seem to form the tumors known as teratomas that sometimes arise from embryonic stem cells implanted in animals.
In the short term, Prentice says, the
new discovery might not have much legislative impact. "I don't think we're going
to see much difference in the rhetoric that both sides will be putting out," he
says, particularly in advance of a bill that Congress may vote on next week.
But, he adds, "people are becoming more aware that there is another way to get
to what we're all after: helping patients, without the ethical concerns and
without the bickering." De Filippo also says the new discoveries would be a boon
to "the momentum of stem-cell research, especially in
Further down the road, the cells could be ideal candidates for "banking," as an increasing number of new parents do today with blood taken from their babies' umbilical cords. Like cord blood cells, the amniotic cells can be frozen. But once thawed, they live much longer. "The maximum you can do with cord blood cells, which are often used to treat leukemia, is get them to double once," says Atala, compared with the stem cells’ lifespan of 250 doublings. A future amniotic stem-cell reserve might be stocked with a variety of genetic types so that cells could be matched to patients with the fewest potential complications.
That era, of course, is well in the future. Many scientists are quick to emphasize that comprehensive human trials are still many years away. It took seven years, Atala notes, just to show the cells' promise, and he declined to estimate how many more it would be before clinical trials could begin, saying, "all those predictions never turn out." There are still many mysteries surrounding amniotic-fluid stem cells—why they don't cause tumors, why they apparently provoke very little immune response when implanted and when during embryonic development they first arise—that might give the FDA pause.
Still, a few experiments on human tissue using cells taken from amniotic fluid are currently in the works. Late last year, a Swiss team reported that it had temporarily been able to grow human heart valves from cells found in amniotic fluid. Dr. Fauza has published a number of large animal studies on tissue engineered from AFS cells over the last several years and is now preparing a clinical trial, this one focusing on children born with a hole in their diaphragms. Babies with the defect today have it patched up with Teflon, "which obviously doesn't grow, so the defect often recurs as the child gets older," says Fauza. Instead, he proposes to construct grafts using amniotic stem cells, and then implant them into newborns. He already has seven years worth of data, all of it encouraging, from performing the same operation on sheep. "The FDA is being helpful, but they are also being very cautious," he says. Still, he hopes the trial will begin in "the not-too-distant future." It's a future that's suddenly looking brighter.
Researchers report alternative stem cell source in amniotic fluid,
avoiding embryo destruction
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AP Photo FX110
By PAUL ELIAS
AP Biotechnology Writer
Scientists reported Sunday they had found a plentiful source of
stem cells in the fluid that cushions babies in the womb and
produced a variety of tissue types from these cells - sidestepping
the controversy over destroying embryos for research.
reported the stem cells they drew from amniotic fluid donated by
pregnant women hold much the same promise as embryonic stem cells.
They reported they were able to extract the stem cells without harm
to mother or fetus and turn their discovery into several different
tissue cell types, including brain, liver and bone.
"Our hope is that these cells will provide a valuable resource
for tissue repair and for engineered organs as well," said Dr.
Anthony Atala, head of
institute and senior researcher on the project.
It took Atala's team some seven years of research to determine
the cells they found were truly stem cells that "can be used to
produce a broad range of cells that may be valuable for therapy."
However, the scientists noted they still don't know exactly how
many different cell types can be made from the stem cells found in
amniotic fluid. They also said that even preliminary tests in
patients are years away.
Still, Atala said the research reported in the scientific
journal Nature Biotechnology expands far beyond similar work
discussed at a heart research conference in November. There, Swiss
researcher Simon Hoerstrup said he managed to turn amniotic fluid
stem cells into heart cells that could be grown into replacement
valves. Hoerstrup has yet to publish his work in a scientific
Atala said the new research has found even more promising stem
cells with the potential to turn into many more medically useful
"We have other cell lines cooking," Atala said.
The hallmark of human embryonic stem cells, which are created in
the first days after conception, is the ability to turn into any of
the more than 220 cell types that make up the human body.
Researchers are hopeful they can train these primordial cells to
repair damaged organs in need of healthy cells.
However, many people, including President Bush, oppose the
destruction of embryos for any reason. The Bush administration has
severely restricted federal funding for the embryo work since 2001,
leading many scientists to search for alternative stem cell
The cells from amniotic fluid "can clearly generate a broad
range of important cell types, but they may not do as many tricks
as embryonic stem cells," said Dr. Robert Lanza, chief scientist
at the stem cell company Advanced Cell Technology. "Either way, I
think this work represents a giant step forward for stem cell
It's the latest advance in the so-called regenerative medicine
field that has sprung
from Atala's lab in
April, Atala and his colleagues rebuilt bladders for seven young
patients using live tissue grown in the lab.
In the latest work, Atala's team extracted a small number of
stem cells swimming among the many other cell types in the amniotic
fluid. One of the more promising aspects of the research is that
some of the DNA of the amnio stem cells contained Y chromosomes,
which means the cells came from the babies rather than the pregnant
said that finding raises the possibility that someday expectant
parents can freeze amnio stem cells for future tissue replacement
in a sick child without fear of immune rejection.
Nonetheless, Daley said the discovery shouldn't be used as a
replacement for human embryonic stem cell research.
"While they are fascinating subjects of study in their own
right, they are not a substitute for human embryonic stem cells,
which allow scientists to address a host of other interesting
questions in early human development," said Daley, who began work
last year to clone human embryos to produce stem cells.
On the Net:
Nature Biotechnology: http://www.nature.com/nbt/index.html
(Copyright 2007 by The Associated Press. All Rights Reserved.)