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Bone marrow transplants may be improved due to the uncovering of a key mechanism

Rehovot, Israel--July 1, 2002--Weizmann Institute scientists have uncovered a key mechanism that enables stem cells to exit the bone marrow into the blood circulation of healthy donors, as well as patients suffering from leukemia, other malignancies and blood disorders. Published in the current July issue of Nature Immunology, the findings may lead to more efficient clinical stem cell transplantations.

Bone marrow transplantation is a last-resort treatment that saves the lives of many patients with cancer and inherited blood disorders. In a transplantation, the patient's malignant or defective stem cells in the marrow are destroyed, and healthy stem cells either from a healthy donor or from the patient himself before or during treatment with chemotherapy must be "encouraged" to come out of the marrow into the bloodstream (in other words, they must be "mobilized"). Thus, scientists have been trying to find out what triggers stem cell mobilization.

Dr. Tsvee Lapidot of Weizmann's Immunology Department, and his PhD student, Isabelle Petit, found that the degradation of SDF-1, a key protein in the bone marrow, is crucial for stem cell mobilization. SDF-1 had previously been found by this and other research teams worldwide to anchor stem cells inside the marrow by activating adhesion molecules (molecules that serve as "glue"). Uncovered today is the "anchors aweigh" mechanism that frees stem cells into the blood.

The scientists investigated stimulation with the growth factor G-CSF, currently the most common clinical method used to induce stem cell mobilization. (In addition to its role in bone marrow transplantation, it is also used to treat children suffering from neutropenia, i.e. lack of white blood cells in the circulation). Before this study, G-CSF's mode of action was largely unknown. Lapidot and Petit found that it reduces the number of SDF-1 proteins in the marrow by causing the production of degrading enzymes, in particular elas
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Contact: Jeffrey J. Sussman
jeffrey@acwis.org
212-895-7951
American Committee for the Weizmann Institute of Science
27-Jun-2002


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