Release of blood stem cells from bone marrow is regulated by brain through human biological clock

Mount Sinai researchers have discovered that the release of blood stem cells from bone marrow is regulated by the brain through the cyclical human biological clock, via adrenergic signals transmitted by the sympathetic nervous system.

These new findings, published online on the website of the journal Nature, point out that the harvest of stem cells for transplantation may be improved by timing it at the peak of their release.

The study describes the mechanisms at the molecular levels in which signals from the biological clock in the brain are sent via the sympathetic—or "fight or flight" branch—of the nervous system, directly to bone marrow stem cell niches. Researchers, using mice as a model, were able to show the rhythmic release and peak of stem cells in circulation during the mouse's resting period, and that changes in the light cycle or an experimental “jet lag” altered the release patterns. This is the first time a study has demonstrated that the brain regulates a stem cell niche.

“We don't know why stem cells circulate in the blood but the maximal release of stem cells in the circulation occurs when the animal is resting. This argues for a role in regeneration,” says Paul S. Frenette, M.D., Professor in the Department of Medicine at Mount Sinai School of Medicine. “More practically, the rhythmic oscillations of circulating stem cells suggest that harvest could be optimized by simply timing the collection of stem cells at the peak of release.”

The vast majority of bone marrow transplantation procedures are currently done using stem cells harvested in the peripheral blood. The current harvesting procedure, however, may not be adequate in some patients, particularly in those that have received prior treatments for cancer.

“What is really amazing to us is that the brain—through the autonomous branch of the nervous system—directly controls stem cells in their microenvironment,” said Dr. Frenette. “An important implication in today's busy world is that changes in normal biological rhythms, for example by working night shifts or a jet lag, could affect the number of stem cells harvested from donors,”

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