Study finds inflammation triggers work by stem cells
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Study finds inflammation triggers work by stem cells
By Bruce Lieberman
UNION-TRIBUNE STAFF WRITER
December 7, 2004
LAURA EMBRY / Union-Tribune
Evan Snyder, a biologist at the Burnham Institute in La Jolla, is a lead author of a study published online yesterday that links inflammation and stem cell activity.
Scientists have known that stem cells restore the body's health by targeting sites of injury and disease, clearing toxins from threatened tissue and replacing dead and dying cells.
But until now, researchers couldn't say exactly how stem cells began this work in the first place.
One answer, proposed in a study published online yesterday, is that stem cells travel to sites of trouble by sensing inflammation.
The finding "could represent a paradigm shift in how we understand how stem cells of many types, from many organs and in many disease states, are programmed to maintain . . . balance within the body," said Evan Snyder, a stem cell biologist at the Burnham Institute in La Jolla and a lead author of the study.
Inflammation spurs an elaborate repair system, Snyder said. It prompts a response in the body that "kills offending organisms, neutralizes toxins and cleans out the terrain," he said.
Stem cells follow, called into action by chemicals released during inflammation.
Yesterday's report – by Snyder and Samia Khoury and Jamie Imitola at Harvard Medical School – illuminates the body's ability to repair itself by using stem cells.
Previous work has shown that stem cells transplanted into an animal will migrate to the site of an abnormality – such as one caused by a stroke, brain disease or cancer tumor.
From there, the cells fight inflammation, reduce scarring, release chemicals called growth factors that promote the health of remaining cells and multiply into replacement cells.
But scientists couldn't pinpoint how the stem cells "knew" where they needed to go.
In the new study, the researchers found that neural stem cells transplanted into the brains of mice homed in on a chemical secreted by injured or inflamed neural tissue.
The chemical, called SDF-1 alpha, acts as a kind of SOS signal to the stem cells. The cells then migrate to the site of injury.
Researchers induced a stroke in the lab animals to create brain damage, subsequent inflammation and the secretion of SDF-1 alpha.
Before implanting neural stem cells into the mice, the scientists incubated the cells with a fluorescent dye so they could later track their movement in the animals.
Once implanted, the stem cells traveled to the injury site and intertwined with cells secreting SDF-1 alpha. The number of stem cells reaching the wound correlated with the amount of SDF-1 alpha secreted.
In a separate experiment, the researchers found that they could reduce the number of neural stem cells reaching areas where SDF-1 alpha was present. To do so, they blocked the stem cells' ability to sense the chemical.
During their experiments, the researchers observed how the neural stem cells moved through a mouse's brain – from where they were implanted to the site of inflammation – by sliding on top of one another.
Each stem cell laid down a path for the next one in a process called chain migration. This movement occurs elsewhere in nature – for example, when a colony of ants moves from its nest to a feeding site.
The chain migration of cells is a well-known phenomenon at all stages of human development. For instance, the olfactory bulb of the brain is believed to develop in this way. Its stem cells migrate upward from deep inside the brain, laying down one layer of cells after another.
New insights into stem cell biology are painting an increasingly complex picture, said Helen Blau, a stem cell researcher at Stanford University.
"We think stem cells can do much more than people have been talking about, (such as) do they convert to the right cell type or do they fuse and rescue the right cell type?" she said.
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Bruce Lieberman: (619) 293-2836; bruce.lieberman@uniontrib.com
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