Stem cells in amniotic fluid show promise

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Stem cells in amniotic fluid show promise

A study finds they offer key therapeutic benefits but avoid

controversy.

By Kaplan, Times Staff Writer

January 8, 2007

http://www.latimes.com/news/nationworld/nation/la-sci-

stemcells8jan08,0,2255075.story?coll=la-home-nation

Researchers have found that some stem cells in human amniotic fluid

appear to have many of the key therapeutic benefits of embryonic

stem cells while avoiding their knottiest ethical, medical and

logistical drawbacks, according to a study published Sunday.

The stem cells — easy to harvest from the fluid left over from

amniocentesis tests given to many pregnant women — were used to

create bone, heart muscle, blood vessels, fat, and nerve and liver

tissues, the study said.

" So far, we've been successful with every cell type we've attempted

to produce from these stem cells, " said study senior author

Atala, director of the Institute for Regenerative Medicine at Wake

Forest University School of Medicine in Winston-Salem, N.C. The

report was published online by the journal Nature Biotechnology.

The finding points to a promising avenue of research that sidesteps

the hurdles facing embryonic stem cell research, which has been

hampered by moral objections to the destruction of embryos that

occurs when the cells are harvested.

The objections have been divisive, prompting President Bush to

restrict federal funding for most human embryonic stem cell

research. Those restrictions have sparked movements in some states

to fund research on their own.

California's Proposition 71, approved in 2004, was designed to

provide $3 billion for stem cell research but has met a vigorous

legal challenge from opponents of the research.

Amniotic stem cell research ducks the controversy because no embryos

are destroyed. The National Institutes of Health already funds such

research.

The study also suggests another advantage: Embryonic cells can form

tumors when implanted in lab animals, but amniotic-fluid stem cells

do not appear to do so.

" If everything that people think about them turns out to be true,

they'll be a powerful source for therapeutic cells, " said Alan

, director of the McGowan Institute for Regenerative Medicine

at the University of Pittsburgh, who wasn't involved in the study.

It is still unclear whether stem cells from amniotic fluid — the

liquid that cushions fetuses in the womb — can produce the range of

cell types that embryonic stem cells can.

" They can clearly generate a broad range of important cell types,

but they may not do as many tricks as embryonic stem cells, " said

Dr. Lanza, an embryonic stem cell researcher and head of

scientific development at Advanced Cell Technology Inc. in

Worcester, Mass.

But even if amniotic stem cells turn out to be less flexible, they

still might be an important tool in the nascent field of

regenerative medicine.

Dr. Dario Fauza, coordinator of the surgical research laboratories

at Children's Hospital Boston, has used the cells to grow tissue to

repair defective diaphragms and tracheas in sheep.

He has asked the Food and Drug Administration for permission to do

the same for children born with herniated diaphragms. It would be

the first human clinical trial involving amniotic stem cells, he

said.

Swiss scientists Dorthe Schmidt and Simon Hoerstrup of University

Hospital Zurich have used amniotic stem cells to grow heart valves.

They are currently testing them in sheep.

The stem cells " may not be as earth-shattering a discovery as human

embryonic stem cells, but these cells could prove to be equally

important for medical therapy, " said Lanza, who was not involved in

the study. " I think this is an exciting breakthrough. "

Amniotic-fluid stem cells lie somewhere between the two major

categories of stem cells: embryonic and adult.

Embryonic stem cells are derived from days-old embryos. Nearly all

of the development is still to come, so those cells must be

extremely flexible.

That " pluripotency " is the reason researchers believe embryonic stem

cells could offer cures for a wide range of ailments. They hope to

use the cells to replace the insulin-secreting islet cells of

diabetes patients and to grow brain tissue to treat stroke victims,

among other treatments. But they don't yet know how.

Adult stem cells are narrowly focused on replenishing specific types

of tissue that wear out over a lifetime, such as skin, hair and

blood. Researchers around the world are looking for ways to expand

the cells' range of capabilities.

Amniotic-fluid stem cells, which are sloughed off by the fetus,

are " a different kind of a stem cell, " Atala said. " It's not as

early as a human embryonic stem cell and it's not as late as the

adult stem cells. "

Scientists surmised more than a decade ago that amniotic fluid would

contain those cells and identified some after several years of

searching.

Atala and his colleagues set out to determine just how plentiful and

flexible the stem cells might be.

The researchers studied 10-milliliter samples of fluid extracted

from pregnant women who had amniocentesis to screen fetuses for

genetic abnormalities. Those tests are commonly performed early in

the second trimester.

Of the myriad cells that make up amniotic fluid, the researchers

found that about 1% had a surface marker that is a hallmark of

embryonic stem cells. They took it as a signal that these cells

might be pluripotent.

The researchers from Wake Forest and Harvard Medical School

biochemically prompted the cells to transform into all of the main

categories of embryonic tissue.

A key test was to see whether the cells functioned like normal cells.

Stem cells induced to become neural cells were able to secrete a

neurotransmitter when stimulated by potassium ions, mimicking

conditions inside the brain, the researchers reported. They also

induced stem cells to develop into liver cells that were able to

secrete urea, a compound produced in the liver.

Other stem cells that had been coaxed into becoming osteoblasts,

which build up bone, were implanted in mice. The cells formed a

tissue that was more dense than normal mouse bone, he said.

" You may be able to obtain the same medical benefits — and cure the

same diseases — without the risks or controversy associated with

embryonic stem cells, " said Lanza of Advanced Cell Technology. " It's

just what the doctor ordered. "

The cells were easy to grow and maintain, and they did not form the

tumors — jumbles of tissue that can include bits of fat, hair and

teeth — that are common with embryonic stem cells, the researchers

said.

" That's one of the biggest issues the FDA will be concerned about

when it comes time to approve stem-cell-based therapies, " said the

University of Pittsburgh's .

But Larry Goldstein, a professor of cellular and molecular medicine

at UC San Diego who studies embryonic stem cells, said the absence

of tumors might signal a limitation of amniotic stem cells. " It

makes me wonder how pluripotent they are, " said Goldstein, who was

not involved in the study.

Though the cells might prove useful in some circumstances, Goldstein

said, they aren't a substitute for embryonic stem cells. " They built

a screwdriver here, but I need a wrench, " he said.

The technology described in the study is owned by Wake Forest

University Baptist Medical Center and controlled by Plureon Corp., a

biotech start-up in Winston-Salem.

Atala serves on Plureon's board and directs its scientific advisory

panel.

The researchers, whose study was primarily funded by the

Frase Foundation and the Crown Foundation of the March of Dimes,

reported they had found similar stem cells in samples of chorionic

villi — a part of the placenta sometimes biopsied as an alternative

to amniocentesis — and of placentas obtained after birth.

Stem cells could one day be routinely extracted from placentas and

stored in case they are needed to create genetically matched tissues

during a baby's lifetime, Atala said. Because the cells would be a

perfect match, the transplanted tissues would not be rejected.

Amniotic-fluid stem cells could also be used to build a stem cell

bank. It would take about 100,000 cell samples to obtain enough

genetic diversity to cover 99% of the U.S. population, he said.