http://www.newscientist.com/news/news.jsp?id=ns99994418

A small company in London, UK, claims to have developed a technique that
overturns scientific dogma and could revolutionise medicine. It says it can
turn ordinary blood into cells capable of regenerating damaged or diseased
tissues. This could transform the treatment of everything from heart disease
to Parkinson's.

If the company, TriStem, really can do what it says, there would be no need
to bother with conventional stem cells, currently one of the hottest fields
of research. But its astounding claims have been met with bemusement and
disbelief by mainstream researchers.

TriStem has been claiming for years that it can take a half a litre of
anyone's blood, extract the white blood cells and make them revert to a
"stem-cell-like" state within hours. The cells can be turned into beating
heart cells for mending hearts, nerve cells for restoring brains and so on.

The company has now finally provided proof that at least some of its claims
might be true. In collaboration with independent researchers in the US, the
company has used its technique to turn white blood cells into the
blood-generating stem cells found in bone marrow.

When injected into mice, these cells migrated to the bone marrow and
generated nearly all the different types of human blood cells, the team will
report in the January edition of Current Medical Research and Opinion (vol
20, p 87), a peer-reviewed journal.


Proof required


"I would be extremely sceptical of these findings and would need more
proof," says stem cell expert Evan Snyder of the Burnham Institute in La
Jolla, California, whose response is typical of many scientists New
Scientist contacted.

"I was extremely sceptical," says team member Tim McCaffrey, a
cardiovascular researcher at George Washington University in Washington DC,
who was asked to evaluate TriStem's claims. "They did it in front of my eyes
with my own blood," he says. "It's stunning."

Even if replacing bone marrow is all TriStem's method can achieve, it is
still significant. Tens of thousands of people need bone marrow transplants
each year. In some cases, doctors already extract stem cells from the blood
instead of transplanting bone marrow itself. A donor is given growth factors
that make their marrow stem cells proliferate and spill over into the blood,
but the procedure takes several days.

TriStem's method might make it possible to obtain vast numbers of blood stem
cells in a fraction of the time. "What's radical is the speed and ease with
which it works," McCaffrey says.


Much, much more


But the company claims it can do much, much more. Ilham Abuljadayel, the
founder of TriStem, says that by adapting standard culturing methods she has
managed to turn white blood cells into heart, nerve, bone, cartilage, smooth
muscle, liver and pancreatic cells.

TriStem has not yet published results proving all these claims. Since the
company has worked only with human cells, it cannot perform what is regarded
as the "gold standard" test of stem cells' versatility: inserting them into
an embryo to show they can form all the different tissues. But if TriStem's
method really can produce a wide range of cells, its potential is huge.

For starters, it would avoid the ethical issues associated with embryonic
stem cells, the most versatile kind of stem cell. TriStem's method would
also make it easy to treat individuals with their own cells, avoiding any
problems with immune rejection. The only way to obtain ESCs that match a
patient's own tissues would be therapeutic cloning, yet to be achieved with
human cells.

The adult stem cells found in various tissues in the body could also solve
both these problems. But there is still much debate about their versatility,
and even if some are capable of forming just about any cell type, they are
scarce. Extracting and multiplying them is difficult and time-consuming.

In addition, TriStem's claims challenge the scientific dogma that
specialised cells cannot revert back to an unspecialised state or be
converted from one type to another. Other groups also claim that they can
"transdifferentiate" cells (New Scientist print edition, 12 October 2002).
But none can do so as swiftly and easily as TriStem.


Killer antibody


Its "miracle" hinges on an antibody manufactured by DakoCytomation of
Denmark that is normally used to detect abnormal brain cells. In the early
1990s, while working as a consultant immunologist, Abuljadayel tried to use
the antibody to kill leukaemia cells. Instead of dying, the cells altered
form and flourished.

Abuljadayel says the antibody binds to a receptor on the cell surface. But
how the antibody triggers "retrodifferentiation", if indeed it does, remains
to be established. To avoid arguments about whether the cells produced are
genuine stem cells, she calls them "stem-cell-like cells".

Abuljadayel applied for a patent on retrodifferentiation in 1994, and in
1999 founded TriStem with the help of her husband, Ghazi Dhoot, then an
investment banker. The company has long struggled to convince mainstream
scientists that its system works.

Like TriStem, McCaffrey encourages sceptics to try the procedure themselves
before condemning it. "I don't think there's voodoo involved, but until a
number of people do it, other scientists have every right to be cautious,"
he says.

For many researchers, alarm bells ring loudest over the failure of TriStem
to get such groundbreaking results published in a leading journal. They also
ask why Abuljadayel has had no permanent academic position.


Gross mortality


Then there is the question of whether TriStem really has achieved
retrodifferentiation. Alexander Medvinsky at the Institute of Stem Cell
Research in Edinburgh thinks the antibody might simply kill ordinary white
blood cells, leaving stem cells behind.

But McCaffrey rejects this, saying that tests show the white blood cells
remain alive. "There is no gross mortality, and the numbers surviving are of
the order of 90 to 95 per cent."

Not all researchers are as sceptical. "The results reported here are
impressive," says Bob Lanza, chief scientific officer of Advanced Cell
Technology of Massachusetts. "If successfully repeated, this process could
have broad clinical potential."

TriStem is sufficiently confident that its method works to start human
trials. Earlier in November it received permission to carry out a clinical
trial of its technology for creating stem cells from blood. Senior
government research collaborators in the country hosting the trial have
asked for the location to be kept secret for now.

The method will be used to treat a dozen patients with aplastic anaemia, a
condition in which people have a severe lack of bone marrow. Abuljadayel
plans to treat the patients with blood stem cells derived from
tissue-matched donors. "Within a week, we should find if the cells have
taken," she says, adding that any improvements in the patients' condition
should be immediately noticeable.



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