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19:00 26 November 03

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.

required Proof

" 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 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. 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.