Time of day influences yield for pharmacologically stimulated stem cell mobilization

Oct 08, 2008

A new study uncovers a previously unrecognized, species-specific impact of circadian rhythms on the production of mobilized stem cells. The research, published by Cell Press in the October 9th issue of the journal Cell Stem Cell, suggests that when it comes to collecting human stem cells for clinical transplantation, picking the right time of day to harvest cells may result in a greater yield.

A variety of organisms have evolved an endogenous timing system, called a circadian clock, to regulate metabolic activities in a day/night cycle. In mice, the cells that give rise to mature blood cells, called hematopoietic stem cells (HSC), are regulated under the influence of rhythmic circadian signals that influence expression of Cxcl12, a gene involved in white blood cell migration.

"Previous research has shown that the "sympathetic" branch of the nervous system, which is involved in stress responses, tightly regulates the amount of Cxcl12 expressed in the bone marrow by circadian oscillation of noradrenaline release. Blood stem cell patterns are basically the mirror image of Cxcl12 expression in bone marrow," says lead study author, Dr. Paul S. Frenette from the Mount Sinai School of Medicine.

Dr. Frenette and colleagues were interested in examining whether circadian time continues to influence mobilization of HSCs when mice are treated with granulocyte-colony-stimulating factor (G-CSF), the most common stem cell mobilizer used in the clinic. The researchers found that after stimulations with G-CSF, synchronization of blood collection with the peak circadian time produced greater HSC recovery. Therefore, even when pharmacological manipulation is used to stimulate HSC mobilization, circadian clock genes continue to influence yield.

The researchers also demonstrated the existence of significant oscillations in the number of human HSCs and found that the circadian rhythm in humans is inverted when compared to that of the mouse. An examination of healthy donors who were contributing HSCs for bone marrow transplantation at Mount Sinai Medical Center between the years of 2000 and 2006 revealed that the average yield was greater for those who underwent the procedure in the afternoon compared with those who were harvested in the morning.

"Our results suggest that the human HSC yield for clinical transplantation might be greater if patients were harvested during the evening compared to the morning," explains Dr. Frenette. "Although prospective clinical studies are needed to ascertain the optimal time for HSC collection, it is possible that a simple adjustment in the collection time may have a significant clinical impact. Further, the maximum release of HSCs at the beginning of the rest period for both species (early night for humans, early morning for mice), supports the intriguing possibility that this phenomenon may contribute to regeneration."

Source: Cell Press

Explore further: New study reveals vulnerability of sharks as collateral damage in commercial fishing

add to favorites email to friend print save as pdf

Related Stories

Working group explores the 'frustration' of spin glasses

15 minutes ago

Spin glasses are frustrating. Although the ideas have been around for decades and form the foundation of countless complex systems models, they have nonetheless resisted researchers' efforts to understand exactly how they ...

The goTenna device pitch is No Service, No Problem

1 hour ago

In the new age of Internet-based crowdfunding with special price offers, where startup teams try to push their product closer and closer to the gate of entry, goTenna's campaign offers a most attractive pitch. ...

Scientists enlist big data to guide conservation efforts

1 hour ago

Despite a deluge of new information about the diversity and distribution of plants and animals around the globe, "big data" has yet to make a mark on conservation efforts to preserve the planet's biodiversity. ...

66-yard crater appears in far northern Siberia

2 hours ago

Russian scientists say they believe a 60-meter (66-yard) wide crater discovered recently in far northern Siberia could be the result of changing temperatures in the region.

Recommended for you

Report on viruses looks beyond disease

1 hour ago

In contrast to their negative reputation as disease causing agents, some viruses can perform crucial biological and evolutionary functions that help to shape the world we live in today, according to a new report by the American ...

Bats use polarized light to navigate

5 hours ago

Scientists have discovered that greater mouse-eared bats use polarisation patterns in the sky to navigate – the first mammal that's known to do this.

User comments : 0