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Biologists cite way to multiply blood stem cells

Cambridge research may aid bone marrow transplants

Biologists announced yesterday a way to dramatically expand populations of blood stem cells, a discovery that could improve bone marrow transplants and make them available to more patients.

Bone marrow transplants save the lives of thousands of Americans every year, mainly cancer patients, but many others are denied treatment because the cells that give the transplants their regenerative power -- blood stem cells -- are quite rare, and doctors have no way of substantially increasing their number before giving a transplant to a patient.

The new technique, discovered in mouse experiments by biologists at the Whitehead Institute for Biomedical Research in Cambridge, uses a cocktail of growth factors to multiply the stem cells up to thirtyfold. If the discovery can be adapted to humans, scientists said, it would transform the field -- saving patients who can't be helped today, in part because of a shortage of bone marrow donors.

''This is a very significant step forward," said Dr. Guy Sauvageau, who was not involved in the Whitehead work and is scientific director of the Institute for Research in Immunology and Cancer in Montreal.

The discovery is also a boon for the field of adult stem-cell research, which has labored in the shadow of its controversial cousin, embryonic stem-cell research. Adult stem cells, such as those that form the blood, do not have the ability to become any cell in the body -- the hallmark of embryonic stem cells. Yet adult stem cells, unlike embryonic ones, are already used to treat patients.

The new research, published yesterday in the journal Nature Medicine, could expand the relatively limited medical uses for adult stem cells.

Stem cells have become the focus of intense research because of their regenerative power. Stem cells can make copies of themselves, and also become more specialized cells, meaning that they can replace damaged tissues. Bone marrow transplants give a patient new blood stem cells, which can then replace red, white, and other blood cells destroyed by chemotherapy or radiation therapy. The transplants are used to treat leukemia, or blood cancer, as well as other diseases such as lymphoma and blood disorders.

One of the most immediate applications of multiplying blood stem cells would be to make the blood taken from umbilical cords at birth more widely usable as an alternative source of stem cells for patients awaiting bone marrow transplants, said Dr. Eva Guinan, associate director for clinical and translational research at the Dana-Farber Cancer Institute. Cord blood has blood stem cells, but not enough to help many adults. Thousands of Americans die every year waiting for a bone marrow transplant.

The technology could also have a wide range of other applications, improving the safety of current procedures and making new ones possible, said Guinan, who is also a bone marrow transplant doctor at Children's Hospital Boston.

For example, it could make it easier to do gene therapy, in which doctors correct genetic problems in blood-forming cells and put the repaired cells in a patient. This could be done, for example, in patients who have severe, inherited diseases of the immune system.

The discovery is also important, scientists said, because it provides new clues into the basic biology of the stem cells. Although these transplants have been used for decades, and blood stem cells are the most intensively studied stem cell, biologists have not been able to accomplish one of the most basic tasks: keeping them alive and healthy outside the body for long periods. This has made them more difficult to study, preventing the expansion of their medical applications, scientists said. The new finding, which coaxed the cells to multiply in laboratory dishes over the course of a week or more, suggests that the field may be coming close to solving this problem.

To find a way to multiply the blood stem cells, the researchers began with nature, according to Cheng Cheng Zhang, a postdoctoral fellow at the Whitehead. When a mouse is developing in the womb, there is a dramatic expansion in the number of blood stem cells near the liver. The same thing happens in humans.

Zhang's team, working under the direction of Whitehead scientist Harvey F. Lodish, suspected that there are cells in the liver that help the blood stem cells multiply. Zhang tried growing blood stem cells next to different types of liver cells, until he found cells that prompted the blood stem cells to multiply, according to the paper, which was published online.

To find out what made these cells special, he compared them with other cells in the liver. He found that these cells were churning out proteins that the other cells were not. He then did another round of experiments, which showed that these proteins, called growth factors, made the blood stem cells multiply.

The most successful cocktail of proteins caused a thirtyfold increase in the number of stem cells, substantially more than similar attempts by other researchers in the past. Some scientists have achieved higher levels by genetically engineering the blood stem cells, but this technique poses a threat of cancer, so would not likely be used by doctors.

Similar growth factors are found in human livers, and the Whitehead team is organizing a study to see whether they can be used to make human blood stem cells multiply in the lab. The work is far from any commercial application because these experiments are difficult and time-consuming. (The team declared no financial interests in the research, according to the paper.) But if the experiments are successful, the next step would be to make sure that all of the growth factors could be used in human cells, without posing any kind of threat. Zhang said he has started new experiments to find more growth factors, with the hope that he can boost the numbers of stem cells even more.

''The more the better," he said.

Gareth Cook can be reached at cook@globe.com.

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