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After 12 days, many hematopoietic stem cells in circulation hadn't incorporated BrdU, meaning that they didn't divide before leaving the bone marrow.
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Like cars circling city blocks on Saturday night, stem cells stand a good chance of finding a parking spot in bone marrow if they circulate long enough. Hematopoietic stem cells frequently leave their niches, freeing up space for other stem cells to enter, report Bhattacharya et al.
Their finding explains a paradox posed by bone marrow transplantations that replaced recipients' blood supplies without radiation treatment. Radiation treatments are normally used in part to clear a recipient's malfunctioning stem cells, thus freeing up limited stem cell space. And although studies suggest that stem cells exit their niches periodically, researchers have thought that the cells first underwent mitosis, leaving a replacement in their wake.
By labeling cells with BrdU, however, the team found that not all hematopoietic stem cells divide before they exit the bone marrow. And they appear to go away often, as one to five hematopoietic stem cells were found in the blood stream of mice at any particular time. The cells circulated for about five minutes—meaning that more than 1,000 stem cells enter circulation each day.
Steady stem cell egress could account for the authors' finding that transplantation was enhanced when mice were given small numbers of donor stem cells repeatedly over seven days as compared with a single large dose.
Although hematopoietic stem cells appear to return to their niche, the extent to which this happens is unknown, as are the signals that drive the cells out or welcome them in. If the factors coordinating this process can be better understood, induced vacancies could provide an alternative to radiation treatments and their accompanying side effects. AM
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