New study sheds more light on blood stem cells biological role

November 30th, 2007 - 6:03 pm ICT by admin  

Washington, Nov 30 (ANI): No other stem cell is understood as thoroughly as the blood, or Hematopoietic Stem Cell (HSC), which have been the driving force behind successful bone marrow transplants for decades. And now, a new study suggests that HSCs biological role is far more versatile and dynamic than thought to be.

Scientists, for the most part, have seen HSCs singular role as that of remaining in the bone marrow indefinitely and replenishing blood and immune system cells only when called upon.

Hematopoietic Stem Cells are occasional and rare cells, scattered sparingly throughout the marrow and capable of replenishing an entire blood system.

A study, led by Ulrich von Andrian, a professor of pathology from the lab of Harvard Medical School, has found that HSCs can travel from the bone marrow, through the blood system, and enter visceral organs where they perform reconnaissance missions in search of pathogenic invaders. Upon encountering an invader they immediately synthesize a defense, divide and mature, churning out new immune system cells such as dendritic cells and other leukocytes, right on the spot.

This process changes the way we look at blood stem cells, said Andrian.

For decades scientists have known that a fraction of HSCs will sometimes migrate from the bone marrow into the bloodstream.

And while scientists have observed this phenomenon, they havent known exactly why the stem cells would do this, and what sort of itinerary they might follow once they entered the blood.

A group in Andrians lab, led by postdoctoral researcher and cardiologist Steffen Massberg, decided to explore this question. They began by extracting lymph samples from the thoracic duct of a mouse.

The thoracic duct, a major component of the lymphatic system, routes the bodys excess fluids into the circulation, fluids that normally accumulate in organs. In that sense, its a kind of physiological storm drainage system.

After screening large samples of thoracic fluid, they discovered an extremely small population of cells that, after rigorous testing, behaved identically to blood stem cells.

Further tests, which involved mice genetically engineered so that their blood stem cells could be detected through fluorescent microscopy, revealed that these cells were also scattered throughout visceral organs, such as liver, heart, and lung.

The researchers had found that the stem cells remain in the tissue for thirty-six hours before exiting into the thoracic duct. This suggested that they were conducting some kind of surveillance. To test this, Massberg and his colleagues injected a bacterial endotoxin into the mouse tissue. Within a matter of days, clusters of specialized immune cells formed in the infected areas.

Typical immune responses deplete local specialized immune cells, said Massberg.

It appears that the hematopoietic stem cells initiate an immune response and replenish these specialized immune cells. Its a way of sensing local environmental disturbances and responding locally, he said.

Finally, the researchers identified the molecular mechanism that explained these observational data.

After residing for a while in the organ tissue, the stem cells receive a lipid signal that enables them to exit into the thoracic duct.

However, the presence of endotoxin disrupts the normal signalling cascade. When the receptors on the stem-cell surface that detect the pathogens become active, the cells ability to receive the lipid signal is blocked. The stem cells literally get stuck in the tissue, where they are then triggered to proliferate into immune cells.

That stem cells are actually a part of the immune system, rather than just giving rise to it, is a very provocative idea, said Andrian.

This opens up a number of new avenues for us to explore ways that our bodies fight pathogens, Andrian added.

The researchers are now looking at ways that other common diseases, like cancer, might exploit this process.

The study is published in Cell. (ANI)

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