Protein primes mouse stem cells to quickly repair injury, study finds

April 18, 2017, Stanford University Medical Center
Credit: martha sexton/public domain

Like drag car racers revving their engines at the starting line, 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 vigor to aging stem .

"We're trying to better understand wound healing in response to trauma and aging," said Thomas Rando, MD, PhD, 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."

Rando, who also directs Stanford's Glenn Center for the Biology of Aging, is the senior author of the study, which will be published April 18 in Cell Reports. Former postdoctoral scholar Joseph Rodgers, PhD, is the lead author. Rodgers is now an assistant professor of and regenerative medicine at the University of Southern California.

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," Rodgers said. "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 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, which exists in a latent form in the spaces between and tissue, can activate a critical signaling 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 isolated from animals with an induced muscle injury. (Mice were anesthetized prior to a local injection of -damaging toxin; they were given pain relief and antibiotics during the recovery period.) After 2.5 days, the researchers found that 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 Rando. "We wanted to know, what is it in the blood that is doing this?"

Increased levels of a protein

The researchers found that the serum from the injured animals had the same levels of HGF as the control serum. However, it did have increased levels of a 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 pretreatment, the researchers found.

In a related experiment, exposing the animals to a single intravenous dose of HGFA alone two days prior to helped the mice recover more quickly. They scampered around on their wheels sooner and their skin healed more quickly than mice that received a control injection. They also regrew their hair around the shaved surgical site more completely than did the control animals.

"Just like in the muscles, we saw the responses in the skin were dramatically improved when the were alerted," Rando said.

In addition to pinpointing possible ways to prepare people for surgeries or other situations in which they might sustain wounds, the researchers are intrigued by the role HGF and HGFA might play in aging. It's known that the pathway activated by these proteins is less active in older people and .

"Stem cell activity diminishes with advancing age, and older people heal more slowly and less effectively than younger people. Might it be possible to restore youthful healing by activating this pathway?" said Rando. "We'd love to find out."

The work is an example of Stanford Medicine's focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.

Explore further: Study identifies cell-cycle phase that primes stem cells for action

Related Stories

Study identifies cell-cycle phase that primes stem cells for action

May 26, 2014
Resting, adult stem cells of many types of tissues enter a reversible "alert" phase in response to a distant injury, according to a study in mice by researchers at the Stanford University School of Medicine.

Stem cells police themselves to reduce scarring

November 28, 2016
Treating mice with a compound that increases the expression of an inactive protein helped them heal from injury with less scarring, according to a study by researchers at the Stanford University School of Medicine.

Why do aged muscles heal slowly?

July 5, 2016
As we age, the function and regenerative abilities of skeletal muscles deteriorate, which means it is difficult for the elderly to recover from injury or surgery. New work from Carnegie's Michelle Rozo, Liangji Li, and Chen-Ming ...

Scientists trigger muscle stem cells to divide

February 23, 2012
(Medical Xpress) -- A tiny piece of RNA plays a key role in determining when muscle stem cells from mice activate and start to divide, according to researchers at the Stanford University School of Medicine. The finding may ...

Regenerating muscle from stem cells

October 28, 2016
A microscopic image of a mouse leg that has been reconstructed with a stem cell transplant shows what may one day help patients regrow new muscle after a major surgery.

Recommended for you

Clues to obesity's roots found in brain's quality control process

February 20, 2018
Deep in the middle of our heads lies a tiny nub of nerve cells that play a key role in how hungry we feel, how much we eat, and how much weight we gain.

Study looks at how newly discovered gene helps grow blood vessels

February 19, 2018
A new study published today found that a newly discovered gene helps grow blood vessels when it senses inadequate blood flow to tissues.

Scientists produce human intestinal lining that re-creates living tissue inside organ-chip

February 16, 2018
Investigators have demonstrated how cells of a human intestinal lining created outside an individual's body mirror living tissue when placed inside microengineered Intestine-Chips, opening the door to personalized testing ...

Data wave hits health care

February 16, 2018
Technology used by Facebook, Google and Amazon to turn spoken language into text, recognize faces and target advertising could help doctors fight one of the deadliest infections in American hospitals.

Researcher explains how statistics, neuroscience improve anesthesiology

February 16, 2018
It's intuitive that anesthesia operates in the brain, but the standard protocol among anesthesiologists when monitoring and dosing patients during surgery is to rely on indirect signs of arousal like movement, and changes ...

Team reports progress in pursuit of sickle cell cure

February 16, 2018
Scientists have successfully used gene editing to repair 20 to 40 percent of stem and progenitor cells taken from the peripheral blood of patients with sickle cell disease, according to Rice University bioengineer Gang Bao.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.