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Blood Could Generate Body Repair Kit
19:00 26 November 03

Exclusive from New Scientist Print Edition

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.

The results should be in by the end of March. Watch this space.

Andy Coghlan

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