Injecting stem cells into the brains of mice that recently suffered a stroke can reduce nerve cell (neuron) damage by up to 60 percent, according to new research.

But the stem cells do not simply replace damaged tissue as previously believed. Instead, the immature cells trigger adult brain cells to switch gears and block a stroke-induced immune response that causes nerve damage.

"It is a paradigm shift," says Sean Savitz, a neurologist at the University of Texas Medical School at Houston, who was not involved in the study. "The original idea is that you put cells in there and it would reconstruct the cells that died. … The beauty of this is there's not just one mechanism; they are acting in many different ways."

Over the past 10 years, he says, research has shown that stem cells have the potential to reduce inflammation, morph into new nerve cells, and stimulate production of fresh blood vessels (to nourish cells) and axons (the long fingerlike projections that neurons use to send information to neighboring cells).

Study co-author Darwin Prockop, director of the Texas A&M University Health Science Center's Institute for Regenerative Medicine, says that previous studies have shown that mesenchymal stromal cells (bone marrow stem cells) can reverse neurodegeneration in the brain caused by disorders such as Parkinson's disease. But scientists were not quite sure how.

"This is the first time really that the mechanisms were laid out," Prockop says.

The finding, published today in Proceedings of the National Academy of Sciences USA, not only promise to pave the way for new therapies but may also help physicians assess the success of these treatments.

Prockop and his team induced strokes in six mice by blocking their carotid arteries, which supply blood to the brain. When blood is cut off cells panic, triggering the immune system, which goes into overdrive, attacking and destroying healthy tissue.

One day after causing the strokes, the researchers injected human mesenchymal stromal cells into the animals' brains. (Prockop says the group used human stem cells because mouse cells are a lot harder to isolate and grow in the lab—though similar results have been seen when animal cells were used.)

"The fascinating thing was the cells were talking to each other—the human cells and the mouse cells," he says. "The human cells turned down some of those inflammatory and immune responses."

Specifically, he says, the stem cells prompted the brain's immune cells (called microglia) to calm down and call off their assault on healthy nerve tissue. This resulted in 60 percent less damage to neurons in the brains of treated animals compared with those who did not receive stem cell infusions. In addition, the treated mice performed better than their untreated peers on a battery of movement, cognitive and behavioral tests.

Prockop says that his team plans more animal tests before trying the procedure on humans. He notes, however, that several biotech companies are currently conducting clinical trials to test the effectiveness and safety of using stem cells to prevent or reverse nerve cell damage. The standard care for stroke today is an enzyme called tissue plasminogen activator that dissolves blood vessel clots and must be given within three hours of an incident. The stem cell method may one day buy doctors additional time to prevent damage to neurons.

Prockop says that mice given the treatment had increased levels of a chemical called galectin 3 in fluid surrounding their brains. "This gives us a way to measure the success of therapy," Prockop says. "We haven't done that in patients yet, but we could look for that."