'Priming' protein boosts stem cell response to injury, promotes healing

Stanford University scientists have identified a protein that, given before an injury, boosts stem cell response and improves healing. “Priming” with this protein, called hepatocyte growth factor activator (HGFA), could eventually speed recovery in cases where injury is expected, such as patients undergoing surgery.

Senior author Thomas Rando and lead author Joseph Rodgers previously showed that injury to one leg caused stem cells in the other leg to become “alert.” This state is different from the fully resting or fully active phases that stem cells usually assume.

To pinpoint the cause of this alert state, the researchers injected uninjured mice with blood serum from mice with a muscle injury. While this serum had the same level of HGF as serum from uninjured mice, it had higher levels of HGFA, a protein that activates HGF. Once HGF is activated, it, in turn, activates a signaling pathway in stem cells that produces proteins that make them alert, according to a statement.

In another experiment, they dosed mice with HGFA two days before injury. The treated mice “scampered around on their wheels” sooner than untreated mice, indicating faster muscle recovery. Their skin also healed faster than that of untreated mice.

“Our research shows that by priming the body before an injury you can speed the process of tissue repair and recovery similar to how a vaccine prepares the body to fight infection,” said Rodgers in the statement.

Finding new ways to stimulate stem cells is a major focus of tissue-repair research. Scientists at New York University and the University of Colorado at Boulder, for example, recently found a gene that prompts adult stem cells to repair injured muscle in mice. They successfully used a drug to boost this gene in mice that did not have it.

While the direct implications of Stanford's discovery are obvious—the treatment could become a way to boost recovery for people in combat or sports, or those who have undergone surgery—the team is also interested in the role of HGF and HGFA in aging.

“Stem cell activity diminishes with advancing age, and older people heal more slowly and less effectively than younger people,” Rando said. The researchers want to look into the possibility of restoring youthful healing rates by activating this pathway, he said.