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1.: Stunning Advance Allows for Reprogramming of Adult Cells From: Stephen Meyer

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1.: Stunning Advance Allows for Reprogramming of Adult Cells

Posted by: "Stephen Meyer" Stephen276@comcast.net stephen_meyer_stemcells

Thu Aug 28, 2008 6:09 am (PDT)

Stunning Advance Allows for Reprogramming of Adult Cells
Research Could Lead to Bevy of Cures, Sidesteps Debate Over Embryonic
Stem Cells

By Rob Stein
Washington Post Staff Writer
Wednesday, August 27, 2008; 1:00 PM

Scientists have transformed one type of fully developed adult cell
directly into another inside a living animal, a startling advance that
could lead to cures for a plethora of illnesses and sidestep the
political and ethical quagmires that have plagued embryonic stem cell
research.

Through a series of painstaking experiments involving mice, the Harvard
biologists pinpointed three crucial molecular switches that, when
flipped, completely convert a common cell in the pancreas into the more
precious insulin-producing ones that diabetics need to survive.

The feat, published online today by the journal Nature, raises the
tantalizing prospect that patients suffering from not only diabetes but
also heart disease, strokes and many other ailments could eventually
have some of their cells reprogrammed to cure their afflictions without
the need for drugs, transplants or other therapies.

"It's kind of an extreme makeover of a cell," said Douglas A. Melton,
co-director of the Harvard Stem Cell Institute, who led the research.
"The goal is to create cells that are missing or defective in people.
It's very exciting."

The findings left other researchers in a field that has become
accustomed to rapid advances reaching for new superlatives to describe
the potential implications.

"I'm stunned," said Robert Lanza, chief scientific officer of Advanced
Cell Technology in Worcester, Mass., a developer of stem cell therapies.
"It introduces a whole new paradigm for treating disease."

"I think it's hugely significant," said George Q. Daley, a stem cell
researcher at Children's Hospital in Boston. "This is a very spectacular
first."

Even the harshest critics of embryonic stem cell research hailed the
development as a major, welcome development.

"I see no moral problem in this basic technique," said Richard
Doerflinger of the U.S. Conference of Catholic Bishops, a leading
opponent of embryonic stems cells because they involve destroying human
embryos. "This is a 'win-win' situation for medicine and ethics."

Melton and other researchers cautioned that many years of research lay
ahead to prove whether the development would translate into cures.

"It's an important proof of concept," said Lawrence Goldstein, a stem
cell researcher at the University of California, San Diego. "But these
things always look easier on the blackboard than when you have do them
in actual patients."

Although the experiment involved mice, Melton and other researchers were
optimistic the approach would work in people.

"You never know for sure -- mice aren't humans," Daley said. "But the
biology of pancreatic development is very closely related in mice and
humans."

Melton has already started experimenting with human cells in the
laboratory and hopes to start planning the first studies involving
people with diabetes within a year. "I would say within five years we
could be ready to start human trials," Melton said.

Other scientists have already started trying the approach on other
cells, including those that could be used to treat spinal cord injuries
and neurogenerative disorders such as Lou Gehrig's disease.

"The idea to be able to reprogram one adult neuron type into another for
repair in the nervous system is very exciting," said Paola Arlotta, who
is working in the Center for Regenerative Medicine at the Massachusetts
General Hospital-Harvard Medical School, in Boston.

The research is the latest development in the explosive field of
"regenerative medicine," which is trying to create replacement tissues
and body parts tailored to patients. That dream appeared within reach
after scientists discovered human embryonic stem cells, which can
develop into any type of cell in the body. But stem cell research has
been plagued by political and ethical debates because the cells can only
be obtained by destroying embryos, which has been opposed by President
Bush and others who believe that even the earliest stages of human life
have moral standing.

Scientists last year shocked the field when they announced they had
discovered how to manipulate the genes of adult cells to turn them back
into the equivalent of embryonic cells -- entities dubbed "induced
pluripotent stem" or "iPS" cells -- which could then be coaxed into any
type of cell in the body.

The new work takes further advantage of the increasing prowess
scientists have developed in harnessing the once mysterious inner
workings of cells -- this time to skip the intermediary step of iPS
cells and directly transform adult cells.

"This experiment proves you don't have to go all the way back to an
embryonic state," Daley said. "You can use a related cell. That may be
easier to do and more practical to do."

Doerflinger argued that the discovery was the latest evidence that
research involving human embryos was no longer necessary.

"This adds to the large and growing list of studies helping to make
embryonic stem cells irrelevant to medical progress," Doerflinger wrote
in an e-mail.

But other researchers disputed that, saying it remains unclear which
approach will ultimately prove most useful.

"Embryonic stem cells offer a unique window in human disease and remain
a key to the long-term progress of regenerative medicine," Melton said.

For their work, Melton and his colleagues systematically studied cells
from the pancreas of adult mice, slowing winnowing the list of genes
necessary to make a "beta" cell that produces insulin. After narrowing
the candidate genes to nine, the researchers genetically engineered
viruses known as adenoviruses to ferry the genes into other pancreatic
cells, known as exocrine cells, which normally secrete enzymes to help
digest food. That finally enabled the researchers to identify the three
crucial genes needed take control of the rest of the cell's genes to
convert an exocrine cell into a beta cell.

"It was a mixture of work, luck and guessing," Melton said. "We achieved
a complete transformation, or re-purposing, of cells from one type to
another. We were delighted."

When the scientists tried the approach on diabetic mice, the animals
became able to control their blood sugar levels.

"It didn't cure the mouse, but . . . they were able to reduce their
blood sugar levels to near normal," Melton said.

Melton and others said it remains to be seen whether it will be
necessary to use genetically engineered viruses, which could face
obstacles getting regulatory approval because of concerns about
unforeseen risks, or whether chemicals might be found to do the same
thing.

If preliminary studies in the laboratory are promising, Melton said he
might first try converting liver cells to insulin-producing pancreatic
cells because that would be safer than the pancreas. An alternative
strategy would be to use the approach to grow beta cells in the
laboratory and transplant them into patients.

Lanza said he was optimistic.

"One day, this may allow the doctor to replace the scalpel with a sort
of genetic surgery," Lanza said. "If this can be perfected, it would
represent one of the Holy Grails of medicine."

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