Medical Chronicle May 2017 | Page 12

NEWS PROTEIN HELPS SPEED WOUND HEALING Pre-treatment with a stem-cell-activating protein significantly enhances healing said Stanford researchers. The approach could eventually help people going into surgery heal better from injuries they sustain. Stem cells respond more quickly to injury when they’ve been previously primed with one dose of a single protein, according to a study from the Stanford University School of Medicine. Mice given the priming protein recover muscle function more quickly after damage, their skin heals more rapidly and even the shaved area around the injury regrows hair more quickly, the study found. Harnessing the power of this protein may one day help people recover more quickly from surgery or restore youthful vigour to aging stem cells. “We’re trying to better understand wound healing in response to trauma and ageing,” said Prof Thomas Rando, Professor of Neurology and Neurological Sciences. “We’ve shown that muscle and bone marrow stem cells enter a stage of alertness in response to distant injury that allows them to spring into action more quickly. Now we’ve pinpointed the protein responsible for priming them to do what they do better and faster.” POTENTIAL THERAPY “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 a fight infection,” said lead author and Assistant Professor of Stem Cell Biology and regenerative medicine at the University of Southern California Prof Joseph Rodgers. “We believe this could be a therapeutic approach to improve recovery in situations where injuries can be anticipated, such as surgery, combat or sports.” Normally, adult, tissue-specific stem cells are held in a kind of cellular deep freeze called quiescence to avoid 12 MAY 2017 | MEDICAL CHRONICLE Rodgers and his colleagues found that a protein can activate a critical signalling pathway in the cells by binding to their surfaces unnecessary cell division in the absence of injury. In a 2014 paper published in Nature, Rodgers and Rando showed in laboratory mice that an injury to the muscle of one leg caused a change in the muscle stem cells of the other leg. These cells entered what the researchers called an 'alert' phase of the cell cycle that is distinct from either fully resting or fully active stem cells. The fact that muscle stem cells distant from the injury were alerted indicated that the damaged muscle must release a soluble factor that can travel throughout the body to wake up quiescent stem cells. Rodgers and his colleagues found that a protein called hepatocyte growth factor (HGF), which exists in a latent form in the spaces between muscle cells and tissue, can activate a critical signalling pathway in the cells by binding to their surfaces. This pathway stimulates the production of proteins important in alerting the stem cells. But it wasn’t known how HGF itself became activated. In the new study, Rodgers and his colleagues identified the activating factor by injecting uninjured animals with blood serum isolated from animals with an induced muscle injury. After 2.5 days, the researchers found that muscle stem cells from the recipient animals were in an alert state and completed their first cell division much more quickly than occurred in animals that had received blood serum from uninjured mice. “Clearly, blood from the injured animal contains a factor that alerts the stem cells,” said Prof Rando. “We wanted to know, what is it in the blood that is doing this?” INCREASED LEVELS OF A PROTEIN The serum from the injured animals had the same levels of HGF as the control serum. However, it did have increased levels of a protein called HGFA that activates HGF by snipping it into two pieces. Treating the serum with an antibody that blocked the activity of HGFA eliminated the recovery benefit of pre-treatment. In a related experiment, exposing the animals to a single intravenous dose of HGFA alone two days prior to injury helped the mice recover more quickly. “Just like in the muscles, we saw the responses in the skin were dramatically improved when the stem cells were alerted,” Prof Rando said.