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Stem cells emerge at night
Posted by Edyta Zielinska
[Entry posted at 8th October 2008 05:47 PM GMT]

Stem cells undergo circadian cycles in humans, emerging from the bone marrow into the bloodstream at higher concentrations at night than in the day, according to a report in Cell Stem Cell this week. The study suggests that a simple change in hospital procedures could significantly increase stem cell yield for therapy.

"We can take advantage of [the findings] if we coordinate our clinical practices" to harvest stem cells for cancer patients late in the day, said author Paul Frenette, a clinical researcher at Mount Sinai School of Medicine.

The work is an update on a paper published online in February by the same group in Nature. In that study, Frenette and his colleagues showed that haematopoietic stem cells (HSCs) leave their niche in mouse bone marrow and travel through the blood during the day -- the mouse's time of rest. A cytokine called CXCL12 expressed by stromal cells in the bone marrow niche signals their movement; when CXCL12 levels go down, HSCs escape into the blood. When the levels increase, the cells return.

HSCs are commonly used to replenish a patient's stem cells which are depleted during cancer thereapy. To determine whether these findings might be meaningful in clinical application, Frenette's group followed up with the current study, in which they examined stem cell cycles in humans. The researchers compared two time-points for HSC harvesting, one at 8am and one at 8pm in normal subjects, and saw a significant increase in HSC levels in the evening harvest.

In practice, patients being treated with autologous HSCs over the course of cancer therapy are first treated with a drug, G-CSF, that forces the stem cells into the blood; the cells are then harvested with plasmapharesis. Frenette's group wanted to know "whether these physiological cycles are maintained? when you force the mobilization with drugs," he told The Scientist. So the researchers compared the number of stem cells they were able to extract from cancer patients who underwent the procedure before 12:30 pm, to those that underwent the procedure before 3:30 pm. Even such a short time period made a difference -- they observed a significant increase in harvest at the later time point.

Current practice in the clinic is to harvest stem cells in the morning, said Frenette, but moving the procedure to afternoon or evening could mean fewer plasmapheresis sessions for patients. It is unclear why the stem cells leave their niche during a patient's time of rest; Frenette speculates that "there might be some function in repair and regeneration," but added that those associations are hard to prove.


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