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Blood could generate body repair kit

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

19:00 26 November 03

Exclusive from New Scientist Print Edition. Subscribe and get 4 free

issues.

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 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. Watch this space.

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