Method boosts bone-marrow transplants
Mouse study offers hope for leukaemia patients.
Researchers have devised a way to improve the success of bone-marrow transplants - the last resort for many patients with leukaemia.
The new technique, which temporarily inactivates a key protein on donor cells, helps transplanted cells home in on the bone marrow and survive there. Although it has yet to be tested in humans, it is hoped that the method will reduce the number of cells needed for therapy, helping limited stores of banked stem cells stretch further.
Leukaemia, a type of blood cancer, affects around 4 out of every 100,000 people worldwide. Chemotherapy and radiation treatment destroy both cancerous cells and healthy, blood-producing stem cells in the bone marrow. Bone-marrow transplants are commonly given during chemotherapy to replace these lost cells.
But tissue-matched donors are hard to come by, so less than a third of patients are eligible for the procedure. Any technique that boosts transplant efficacy would be extremely useful.
Hal Broxmeyer from Indiana University School of Medicine, Indianapolis, and colleagues isolated bone-marrow stem cells from mice, then treated them with a chemical that prevents an enzyme, called CD26, from working.
CD26 makes it difficult for injected cells to migrate to their final destination. Treated cells, injected into the veins of mice lacking bone-marrow stem cells, were twice as likely to reach the bone marrow compared with untreated cells.
The technique more than doubled the survival of donor cells in the bone marrow, and of the recipient animals themselves. The results are reported in this week's edition of Science1.
"This is a very important discovery," says David Bodine of the National Human Genome Research Institute in Bethesda, Maryland, who studies the development of blood cells. "Overcoming the inefficient homing of stem cells will allow transplants to be done with fewer cells."
If the technique works for humans, Broxmeyer hopes that cells from one donor could be used to treat more than one compatible patient. At present, the large number of cells needed for grafting mean that this is not possible.
The method could also be used to enhance the effectiveness of umbilical-cord stem-cell transplants. Transplants of umbilical-cord blood, which also contain blood-producing stem cells, are sometimes given when donor-matched bone-marrow stem cells cannot be found. The tissue's immature status means it is less likely to be rejected, so it is useful for a broader range of recipients.
Although hundreds of thousands of cord blood samples are stored in banks worldwide, each sample is very small (up to 200 millilitres) and is unlikely to contain enough stem cells for an efficient transplant.
If we can knock out CD26 in cord blood stem cells, we may be able to boost their transplant efficiency, says Broxmeyer. This means that more patients could be treated with the limited, banked samples.
- Christopherson II K. W., Hangoc G., Mantel C. R. & Broxmeyer H. E. Science, 305. 1000 - 1003 (2004).
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