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This week at the AAAS : Seek and destroy - Eliminating problem cells improves prospects for transplants

点击量:   时间:2017-08-07 08:01:03

By Nell Boyce PEOPLE who desperately need a bone marrow transplant could benefit from a technique that makes a perfectly matched donor unnecessary. If the marrow transplants are successful, then eventually patients who have kidney or heart transplants might be spared a lifelong course of drugs to prevent rejection of their new organ. Bone marrow stem cells—a type of blank blood cell—give rise to all the different cells that make up the immune system. This means that patients with leukaemia and other diseases of these cells can sometimes be cured by destroying most of their existing marrow with radiation and chemotherapy, and replacing it with marrow from a donor. Unfortunately, donated cells can attack the patient’s body, causing life-threatening graft-versus-host disease. This happens when there are too many differences between certain proteins called HLA antigens on the outside of the patient’s cells and the donor’s cells. HLA antigens trigger an immune response to foreign tissue. Most patients receive bone marrow transplants from a brother or sister, who are more likely to share the six key HLA antigens. But even then, 40 per cent of patients will suffer from graft-versus-host disease. When fewer than four of the antigens match, the death rate is around 80 per cent. Suzanne Ilstad, a transplant surgeon at the Allegheny University of the Health Sciences in Philadelphia, has come up with an alternative approach. Graft-versus-host disease is triggered by mature T cells that are transplanted along with the stem cells. So Ilstad has developed ways to screen out these cells, while increasing the proportion of other cells, called facilitating cells, that help the marrow graft into the patient’s bones. The technique depends on the ability to recognise molecular markers on the surface of the facilitating and T cells. Last April, Ilstad started a clinical trial with desperately ill leukaemia patients who had no hope of finding a perfectly matched donor and were willing to risk a mismatched transplant. Of 25 patients taking part in the trial, none has rejected their graft. While the first patients did develop chronic graft-versus-host disease, further refinements of the separation technique, which enable Ilstad to strip out the immune cells, seem to have solved the problem. Ilstad is now planning a larger trial of the technique. Following her success with marrow grafts, Ilstad has moved on to solid organ transplants. Animal studies have shown that if an organ is transplanted along with marrow from the same donor treated with Ilstad’s separation method, the recipient’s modified immune system will not attack the new organ. When other transplant surgeons have tried to give mismatched bone marrow the stem cells failed to graft because researchers had stripped out the facilitating cells along with the damaging T cells. After reviewing Ilstad’s results with the leukaemia patients, the US Food and Drug Administration earlier this month decided to let her try the new technique in around a dozen patients receiving kidney or heart transplants. “At the same time the organs are harvested, we will also extract bone marrow cells,” says Ilstad. The researchers will then modify the marrow as they did in the leukaemia trial. “Once the organ is in place, we will infuse the bone marrow,