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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.

WEB EXCLUSIVE

By Mary Carmichael

Newsweek

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 Wake Forest University who led the research team. (The study appears in the journal Nature Biotechnology.) The "AFS cells" rival embryonic stem cells in their ability to multiply and transform into many different cell types, and they eventually could be hugely helpful to doctors in treating diseases throughout the body and building new organs in the lab. At the same time, the amniotic cells can be taken easily and harmlessly from the placenta or from pregnant women by amniocentesis—which gives them the potential to nullify, or at least bridge, the divide in the stem-cell-research debate. One out of every 50 pregnant women undergoes amniocentesis, a procedure that tests the fetus for genetic defects, and about 1 percent of the cells collected by amniocentesis are stem cells. What's more, the stem cells are also found in the placenta, which is thrown away after birth—so doctors may obtain them from all infants, not just those subject to amniocentesis.

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 California."

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.

URL: http://www.msnbc.msn.com/id/16513279/site/newsweek/

BC-Stem Cells,0770

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.

      Researchers at Wake Forest University and Harvard University

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 Wake Forest's regenerative medicine

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

journal.

      Atala said the new research has found even more promising stem

cells with the potential to turn into many more medically useful

replacement parts.

      "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

sources.

      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

research."

      It's the latest advance in the so-called regenerative medicine

field that has sprung from Atala's lab in Winston-Salem, N.C. 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

moms.

      Dr. George Daley, a Harvard University stem cell researcher,

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:

      Wake Forest regenerative medicine institute:

http://www.wfirm.org/

      Nature Biotechnology: http://www.nature.com/nbt/index.html

      (Copyright 2007 by The Associated Press.  All Rights Reserved.)