Embryonic Stem Cells Save Ailing Mouse Embryos
By SUSANNE QUICK - [log in to unmask]

Posted: Oct. 7, 2004

Potentially turning a hot ethical battle on its head, researchers have saved embryos
by destroying embryos.

Scientists at the Memorial Sloan-Kettering Cancer Center in New York reported that
they were able to save mouse embryos destined to die from a genetic heart defect
by injecting them with mouse embryonic stem cells.

The "embryonic stem cells completely rescued" the pups and their heart defects,
said Robert Benezra, the study's senior author and a researcher at the center's
cancer biology and genetics program. "This was a complete surprise."

"We are witnessing the birth of a new science here," said Richard Schatz, co-chief
of cardiologyat the Scripps Clinic in La Jolla, Calif.

However, Schatz, who is conducting his own trial using adult stem cells on patients
with severe angina, cautioned that treatments that work well in animals don't always
work in humans.

"It's incredible," said Arthur Caplan, a professor of medical ethics at the University
of Pennsylvania.

This research shows "promise that stem cell research is setting on a new course,"
he said. And it will have a direct impact on the current stem cell debate.

However, Gary Lyons, a professor of anatomy at the University of Wisconsin
Medical School, cautioned that although "this is an important discovery," it is "not
big news in the stem cell world."
'Fascinating'

Work conducted previously by Benezra and his colleagues showed a relationship
between a protein called Id and the normal development of capillaries and blood
vessels.

They demonstrated this by engineering strains of mice that lacked genes to code for
Id. These mice, called "knockouts," displayed severe cardiac defects and died
before birth.

In this latest research, the cancer center scientists wanted to see whether
embryonic stem cells would influence heart development in the knockouts. So they
injected stem cells into early embryos - embryos so young their hearts had not yet
developed.

The thinking was that embryonic stem cells - the templates of all organs, tissue and
body parts - might influence cardiac development.

It did, but in ways the researchers hadn't anticipated.

According to Benezra, the stem cells did not change the knockout mice's DNA.
Instead, they influenced the young mice's ability to express certain genes.

"It was fascinating," he said.

"We observed that the stem cells provided normal signals to themselves and also to
the neighbor cells to correct the organ as a whole," said Diego Fraidenraich, the
study's lead author and a cancer center researcher.

"In other words, stem cells act like nurses, restoring 'sick' cells to health," Benezra
said.

And they did so with astounding effects: 100% of the embryos were born alive, and
50% lived to be at least 1 year old - a healthy middle age for lab mice.

The researchers also injected embryonic stem cells into female mice, which were
then impregnated with knockout mice.

And these females gave birth to some pups whose hearts were partially corrected:
an indication that embryonic stem cells secrete factors across the placenta.

It didn't work as well as injecting the stem cells directly into the embryos, said
Benezra, but was still exciting.

"No one has ever done anything like this before," he said. The work, he said, is
revolutionary.
Tempered reactions

Lyons, the UW researcher, was more tempered in his reaction. Lyons said such
injections have been done before, and the embryonic stem cells are probably not
required to show the effects demonstrated.

Indeed, in the case of injections into the mother, the molecules secreted by the stem
cells could be introduced without them.

The embryonic stem cells made a molecule called IGF1, which was missing in the
ill-fated pups, he said. "Replacing that signaling molecule" allowed the "mice to
survive in the context of the uterus, but these mice were not viable outside the
womb."

Still, others are excited.

Including Kenneth Chien, a University of California, San Diego researcher. He said
the study "expands the potential therapeutic repertoire" of embryonic stem cells.

And he thinks scientists now should test whether such molecules also might treat
adult heart disease.

Caplan, the University of Pennsylvania bioethicist, believes Benezra's research may
also open doors to treating "new disease groups not included in the fight so far."

Indeed, while embryonic stem cells have been touted as possible cures for diseases
such as Parkinson's and spinal cord injuries, this new research holds the promise of
curing genetic and congenital diseases.

It's this potential that Caplan and Robyn Shapiro, director of the Center for the
Study of Bioethics at the Medical College of Wisconsin, find most exciting.

These kinds of diseases, said Caplan, are the most difficult to deal with.

"You can't just kill the virus" in these cases. Instead doctors end up "patching and
filling," and doing the best they can to help children born with genetic disorders.

"This is speaking to life itself," said Shapiro, "the absence of disability is a real
possibility" with this kind of research.

They both cautioned that the work may not translate to other animals and humans.

But this new research may change the way scientists approach genetic diseases,
Caplan said.

"This is awesome," he said.

John Fauber of the Journal Sentinel staff and the Associated Press contributed to
this report.

From the Oct. 8, 2004, editions of the Milwaukee Journal Sentinel

SOURCE: Milwaukee Journal Sentinel, WI
http://www.jsonline.com/news/nat/oct04/264979.asp

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