A SMALL company in London 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鈥檚.
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鈥檚 blood, extract the white blood cells and make them revert to a 鈥渟tem-cell-like鈥� state within hours. The cells can be turned into beating heart cells for mending hearts, nerve cells for restoring brains and so on.
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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.
鈥淚 would be extremely sceptical of these findings and would need more proof,鈥� says stem cell expert Evan Snyder of the Burnham Institute in La Jolla, California, whose response is typical of many scientists New 杏吧原创 contacted.
鈥淚 was extremely sceptical,鈥� says team member Tim McCaffrey, a cardiovascular researcher at George Washington University in Washington DC, who was asked to evaluate TriStem鈥檚 claims. 鈥淭hey did it in front of my eyes with my own blood,鈥� he says. 鈥淚t鈥檚 stunning.鈥�
Even if replacing bone marrow is all TriStem鈥檚 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鈥檚 method might make it possible to obtain vast numbers of blood stem cells in a fraction of the time. 鈥淲hat鈥檚 radical is the speed and ease with which it works,鈥� McCaffrey says.
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 鈥済old standard鈥� test of stem cells鈥� versatility: inserting them into an embryo to show they can form all the different tissues. But if TriStem鈥檚 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鈥檚 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鈥檚 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 (see 鈥淢any claims 鈥� how many cells?鈥�), they are scarce. Extracting and multiplying them is difficult and time-consuming.
In addition, TriStem鈥檚 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 鈥渢ransdifferentiate鈥� cells (New 杏吧原创, 12 October 2002, p 38). But none can do so as swiftly and easily as TriStem.
Its 鈥渕iracle鈥� 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 鈥渞etrodifferentiation鈥�, if indeed it does, remains to be established. To avoid arguments about whether the cells produced are genuine stem cells, she calls them 鈥渟tem-cell-like cells鈥�.
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. 鈥淚 don鈥檛 think there鈥檚 voodoo involved, but until a number of people do it, other scientists have every right to be cautious,鈥� 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.
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. 鈥淭here is no gross mortality, and the numbers surviving are of the order of 90 to 95 per cent.鈥�
Not all researchers are as sceptical. 鈥淭he results reported here are impressive,鈥� says Bob Lanza, chief scientific officer of Advanced Cell Technology of Massachusetts. 鈥淚f successfully repeated, this process could have broad clinical potential.鈥�
TriStem is sufficiently confident that its method works to start human trials. Earlier this month 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. 鈥淲ithin a week, we should find if the cells have taken,鈥� she says, adding that any improvements in the patients鈥� condition should be immediately noticeable.
The results should be in by the end of March. Watch this space.
Many claims 鈥� how many cells?
IF TRISTEM鈥檚 claims hold up to scientific scrutiny, we may have an easily accessible source of stem cells running through our veins. But what does this mean? After all, in recent years several teams have reported that highly versatile stem cells can be extracted from adult tissues such as the skin, bone marrow, muscle, fat and even teeth.
TriStem says its cells are different, claiming that its method somehow makes white blood cells regress to a more stem-cell-like state. Other groups 鈥� most notably Catherine Verfaille鈥檚 at the University of Minnesota 鈥� say that they can select and expand a very rare population of versatile stem cells already present in adult tissues, through several rounds of cell culture.
In all cases, cells are taken out of their natural environment and manipulated until they exhibit characteristics similar to embryonic stem cells. Is it possible that, although they start with different materials or use different methods, all groups have arrived at the same end product?
It鈥檚 a crucial question because it will determine who owns the patent rights. While some people believe stem cells should not be patentable, in the US most groups have rushed to patent their cells based on their surface characteristics. They could be on dodgy ground, because cell surface characteristics can change when culture conditions change. Already, one large biotechnology company is challenging the claim that these cells are all distinct (New 杏吧原创, 17 May, p 12).
Other groups, like Verfaille鈥檚, have patented the methods used to extract the cells. But some experts suspect that instead of isolating stem cells from bone marrow, her team鈥檚 procedure actually generates the stem cells. If this turns out to be the case, TriStem could reap the benefits. Its patents, which pre-date others, are very broad, claiming rights to all means of preparing 鈥渦ndifferentiated cells鈥� from specialised ones.
Such issues are likely to lead to fierce patent disputes, given the vast amounts of money at stake. Lawyers may well be the first to profit from stem cell technologies.
Sylvia Pag谩n Westphal