Stem Cells May Offer Stroke-Damaged Brain Protection Against Itself

by Aalok Mehta

October 13, 2008

Stem cells can drastically reduce the amount of damage following a stroke by limiting the body’s natural “overreaction” to the trauma, a new animal study has found.

Scientists have long known that stem cells seem to offer some protection against stroke damage, but how they did it was not clear. Perhaps the stem cells replace the dying neurons and replicate their functions, many experts suggested.

But stem cells instead appear to alter the expression of dozens of genes to dramatically tamp down the body’s immune and inflammatory responses, according to research by Darwin Prockop, director of the Texas A&M University Health Science Center's Institute for Regenerative Medicine, and colleagues.

While these reflexive responses help the body recover from injury, they also coax immune cells to damage or destroy nearby healthy tissue, a particular problem for sensitive brain cells.

“These responses are excessive—off the scale,” Prockop says. “If you can tone down some of these, you can avoid many of the terrible effects of stroke.”

Prockop and his team blocked blood flow through the carotid artery in mice to cause a stroke. A day later, the researchers implanted stem cells derived from human bone marrow. The treatment reduced the overall neuron damage by 60 percent compared with that seen in untreated animals.

The stem cells altered the expression of more than 10 percent of the approximately 600 genes activated during stroke recovery, many of them directly related to immune and inflammatory responses, the team found.

“This is a new paradigm for how stem-like cells work. They’re not replacing cells, though they can do that in a limited amount.” Prockop says. “It’s really about repairing cells rather than replacing them. That we can stop injured tissue from destroying itself—that was a big surprise.”

The results appeared in a paper published online by the Proceedings of the National Academy of Sciences on Sept. 15; the research was conducted while Prockop was a biochemistry professor at Tulane University.

‘Cross-talk’ among species

The research offers several other unexpected findings that raise hopes for an eventual human treatment, Prockop says.

For one, human cells had a drastic effect in mice and expressed a different set of genes in mice brains than when raised in culture. “It shows that there is cross-talk in effect,” he says. “Mouse cells are talking to human cells, and human cells are talking to mouse cells.”

The stem cells also reduced damage even though they were implanted 24 hours after the stroke, extending the window in which treatment could be used, Prockop says.

Finally, the stem cells did not integrate themselves into the brain but largely disappeared within a week of being added. This limits the chances for long-term side effects, which is a concern because earlier studies have found that bone marrow stem cells seem to accelerate the progress of certain cancers.

Prockop hopes to conduct additional animal studies and eventually clinical trials in humans.

Possible human applications far down the road

“This is a nice paper with some new data,” says Eva Mezey, head of the Adult Stem Cell Research Section at the National Institute of Dental and Craniofacial Research. “It’s the first time someone has shown differences in gene expression.”

But though stem cells are in clinical trials for some conditions, such as graft-versus-host disease, she warns that stroke may be a much more difficult target.

“Unfortunately, so far there are no good mouse models for stroke,” she says. “We should be very careful not to raise hopes in stroke victims. Even if this works in people, it’s years and years away.”

In the meantime, researchers continue to explore various ways to harness stem cells effectively in the fight against brain and nervous system diseases.

The biotech company ReNeuron, for example, is petitioning to begin clinical trials of its stem cell lines—including some neural cells—within the next year.

A recent article in the Journal of Biology outlined a method for preparing and testing stem cells to optimize treatment of spinal cord injuries.

And the University of Adelaide recently opened a new stem cell research center, with the stated goal of releasing results by the end of the year outlining whether stem cells from adult teeth can help repair stroke damage.