Loss of SDF-1 Triggers Stem Cell Mobilization

Research into the factors that initiate stem cell migration from the bone marrow into circulation has revealed that degradation of stromal cell-derived factor 1 (SDF-1), a protein involved in binding stem cells within the bone marrow, is crucial for stem cell mobilization. The research results were reported in the July 2002 issue of Nature Immunology.

The current studies were carried out using an experimental system developed in 1999 at the Weizmann Institute of Science (Rehovot, Israel) in which human stem cells are transplanted into a line of immune-suppressed mice. Treatment with the growth factor G-CSF, currently the most common clinical method used in human patients, was used to induce stem cell mobilization.

The Weizmann investigators found that G-CSF reduced the amount of SDF-1 in the marrow by promoting synthesis of degrading enzymes, in particular neutrophil elastase. Stem cell mobilization peaked when SDF-1 levels in the bone marrow were at their lowest.

The researchers also found that G-CSF caused an increase in the number of CXCR4 receptors on stem cells and maturing white blood cells in the bone marrow. CXCR4 is the receptor that binds specifically with SDF-1. Interaction between SDF-1 and CXCR4 was necessary for mobilization to take place, since treatment with either anti-SDF-1 or anti-CXCR4 neutralizing antibodies blocked stem cell mobilization.

The authors hope that their findings may lead to improved collection of stem cells for clinical transplantations.




Related Links:
Weizmann Inst.