To investigate further, the team analyzed genetic activity in samples of brain tissue before and after stem-cell injection. They found that 586 genes in the mouse brain were overactive in following brain injury and that 10 percent of these genes were dampened after stem-cell injection. Prockop found that many of these genes produce proteins involved in inflammation and immunity, and he hypothesizes that stem cells actually change the genetic instructions given out by brain cells in response to injury, reducing brain swelling that would otherwise occur.
To confirm the findings, the team also examined mouse brains for cytokines–proteins secreted by immune cells in response to injury. These proteins come in a variety of forms that can induce either inflammatory or anti-inflammatory effects. The researchers found that, following stem-cell injection, the affected brain area was flooded with insulin-like growth factor 1–an anti-inflammatory cytokine secreted by immune cells that protects the brain from blood-deprived injury, such as stroke. Other proteins indicating the presence of immune cells were also found in increased numbers, compared with untreated brain samples.
Identifying the various proteins that reduce inflammation could lead to new drugs that increase the production of such proteins to treat a variety of diseases, Prockop says. However, he believes that stem cells themselves may ultimately be a more effective therapeutic route. “You could find out all the proteins that are made, and give those to patients,” says Prockop. “But you may get a better response with stem cells, because they have this marvelous ability to sense and adjust to their environment.”
Eva Mezey, a National Institute of Health investigator who studies stem-cell interactions in the brain, agrees that stem cells may have broad applications in treating inflammation but cautions that they may not be the most effective therapy for stroke. “Almost every stroke is a little bit different, and a person may have other diseases, like diabetes,” Mezey says. “There are so many other variables that it seems there isn’t one drug that’s efficacious in humans.”
She adds that “stem cells may be a very promising new way in the treatment of a variety of diseases that are somehow related to immunity or inflammation, but they are not a therapy for stroke.”