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Bones hold the key to blood renewal

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Department, which included Dr. Orit Kollet and colleagues, found that the bone-dismantling osteoclasts are instrumental in releasing hematopoietic stem cells into the bloodstream. As they wear away the bone, they allow the stem cells out of the niches and into the bloodstream. Although some hematopoietic stem cells can always be found circulating in the blood, when there is bleeding or inflammation in the body, more stem cells are needed to deal with the situation and restore balance. The team's study showed that the bone marrow response to the body's call for help involves stepping up production of osteoclasts, putting machinery that normally operates at a leisurely pace into high gear. The osteoclasts not only clear away bone, they also break up 'nurturing' substances in the niche that attract and hold the stem cells to that spot, thus allowing more stem cells into the bloodstream.

The team carried out their research on mice, including some developed in the lab of Prof. Ari Elson of the Molecular Genetics Department, in which the osteoclasts carried a mutation that rendered them only partially functional in the young females. They found abnormally low stem cell levels in the blood of these mice even when they tried to encourage their mobilization, giving them solid evidence of the connection. In normal mice, using a chemical compound that stimulates osteoclast formation, they were able to boost osteoclast levels and thus manage the release of stem cells into the blood in a variety of stress situations. This finding may have implications for bone marrow transplant techniques: The drugs given today to donors to increase the supply of stem cells in their bloodstream before they are harvested for transplantation cause the release of many other mature cells as well. Injecting the osteoclast-promoting substance into the mice, on the other hand, resulted in an increase mainly in stem cell release. These findings add a new dimension to our understanding of
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Source:American Committee for the Weizmann Institute of Science


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