http://www.sciscoop.com/story/2003/11/29/4520/0469
Major Breakthrough In Disease Treatment Via Stem Cells Claimed
By rickyjames, Section News
Posted on Sat Nov 29th, 2003 at 04:52:00 AM PST
It sounds too good to be true, and most scientists think that it is.
But the greatest thing about science is that if you and others can
reproduce the most outlandish of claims in a lab, acceptance of your
ideas and discoveries will (probably, slowly) occur. That appears to
be the process that British company TriStem is undergoing with
upcoming publication in January of its latest research in the
peer-reviewed Current Medical Research and Opinion (vol 20, p 87).
This paper marks the first time TriStem's work has been cleared by
unbiased scientist-referees for publication in a respected, mainstream
medical journal.
Tristem is claiming it has developed a process to convert
easily-isolated white blood cells into stem cells which it can further
culture to replace any defective tissue in the body. Current
scientific dogma holds that once a stem cell has differentiated into
mature body tissue like a blood cell, the transformation cannot be
reversed. TriStem says it can. If true, not only has TriStem bypassed
the current need to obtain stem cells from human embryos for research;
it has revolutionized the very foundation of medicine. To say that
other scientists have been sceptical of TriStem's claims is an
understatement. "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.
And yet, TriStem has apparently taken white blood cells of lab mice,
converted them back into stem cells, further treated the stem cells to
make them into blood-producing bone marrow cells, and injected the new
bone marrow cells into the bones of the mice, where the cells took up
the duty of making blood. All of this research effort was performed
under the watchful eye of a third-party U.S. research laboratory team,
which acted as a critic - and came away convinced thay had seen the
future of medicine. "I was extremely sceptical," says team member Tim
McCaffrey, a cardiovascular researcher at George Washington
University. "They did it in front of my eyes with my own blood. It's
stunning. What's radical is the speed and ease with which it works."
This technique alone, if confirmed, could revolutionize bone marrow
transplants and leukemia therapy. Yet TriStem claims this is only the
beginning of what it can do...
In currently unpublished research, TriStem founder Ilham Abuljadayel
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. If true, this is a stunning
achievement that could lead to diverse treatments ranging from a cure
to diabetes to liver regeneration to heart attack recovery to healing
spinal cord injury.
The key to TriStem's "transgeneration" technique is a special antibody
manufactured by DakoCytomation of Denmark that is normally used to
detect abnormal brain cells. A decade ago Abuljadayel tested this
antibody as a possible treatment for leukemia. Instead of killing
leukemia-diseased white blood cells, the drug caused them to flourish
- and undergo spectacular alterations Abuljadayel dubbed
"retrodifferentiation" and promptly patented. She's been developing
the technique ever since. 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.
Growing trust in TriStem's claims is quickening the pace of its
progress. Earlier this month the company received approval from an
unnamed government to begin human trials of the
blood-to-implanted-bone-marrow process. Because of the hoopla
surrounding the effort, this trial is being held in secret in the
unidentified host country. A dozen patients with aplastic anemia
(severe bone marrow deficiencies) are to be treated in the trial.
"Within a week [of implantation], we should find if the [Tristem]
cells have taken," Abuljadayel says. Improvements in the patients'
condition should be immediately noticeable, and results are
anticipated to be announced in March. Stay tuned.
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http://www.newscientist.com/news/news.jsp?id=ns99994418
Blood could generate body repair kit
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.
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