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

Byproducts of 'junk DNA' implicated in cancer spread

August 14, 2018
The more scientists explore so-called "junk" DNA, the less the label seems to fit.

Doctors may be able to enlist a mysterious enzyme to stop internal bleeding

August 14, 2018
Blood platelets are like the sand bags of the body. Got a cut? Platelets pile in to clog the hole and stop the bleeding.

Artificial placenta created in the laboratory

August 14, 2018
In order to better understand important biological membranes, it is necessary to explore new methods. Researchers at Vienna University of Technology (Vienna) have succeeded in creating an artificial placental barrier on a ...

Using DeepMind's neural network learning system to diagnose eye diseases

August 14, 2018
Three institutions working together have applied DeepMind's neural network learning system to the task of discovering and diagnosing eye diseases. Moorfields Eye Hospital has been working with Google's DeepMind Health subsidiary ...

3-D printed biomaterials for bone tissue engineering

August 13, 2018
When skeletal defects are unable to heal on their own, bone tissue engineering (BTE), a developing field in orthopedics can combine materials science, tissue engineering and regenerative medicine to facilitate bone repair. ...

Artificial intelligence platform screens for acute neurological illnesses

August 13, 2018
An artificial intelligence platform designed to identify a broad range of acute neurological illnesses, such as stroke, hemorrhage, and hydrocephalus, was shown to identify disease in CT scans in 1.2 seconds, faster than ...

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.