From Hopkins: “Johns Hopkins biologists find protein that bolsters growth of damaged muscle tissue”

Johns Hopkins
Johns Hopkins University

Jul 19, 2016
Arthur Hirsch

Johns Hopkins University biologists have found that a protein that plays a key role in the lives of stem cells can bolster the growth of damaged muscle tissue, a step that could potentially contribute to treatments for muscle degeneration caused by old age and diseases such as muscular dystrophy.

The results, published online by the journal Nature Medicine, show that a particular type of protein called integrin is present on the stem cell surface and used by stem cells to interact with, or “sense,” their surroundings. How stem cells sense their surroundings, also known as the stem cell “niche,” affects how they live and last for regeneration. The presence of the protein β1-integrin was shown to help promote the transformation of those undifferentiated stem cells into muscle after the tissue has degraded and improve regenerated muscle fiber growth as much as 50 percent.

While the presence of β1-integrin in adult stem cells is apparent, “its role in these cells has not been examined,” especially its influence on the biochemical signals promoting stem cell growth, wrote the three authors—Chen-Ming Fan, an adjunct biology professor at Johns Hopkins; Michelle Rozo, who completed her doctorate in biology at Hopkins this year; and doctoral student Liangji Li.

The experiment shows that β1-integrin—one of 28 types of integrin—maintains a link between the stem cell and its environment, and interacts biochemically with a growth factor called fibroblast growth factor (FGF) to promote stem cell growth and restoration after muscle tissue injury. Aged stem cells do not respond to FGF, and the results also show that β1-integrin restores aged stem cell’s ability to respond to FGF to grow and improve muscle regeneration.

By tracking an array of proteins inside the stem cells, the researchers tested the effects of removing β1-integrin from the stem cell. This is based on the understanding that the activities of stem cells—undifferentiated cells that can become specialized—are dependent on their environment and supported by the proteins found there.

“If we take out β1-integrin, all these other [proteins] are gone,” Fan, the study’s senior author and a staff member at the Carnegie Institution for Science in Washington and Baltimore, said in an interview.

Why that is the case is not clear, but the experiment showed that without β1-integrin, stem cells could not sustain growth after muscle tissue injury.

By examining β1-integrin molecules and the array of proteins that they used to track stem cell activity in aged muscles, the authors found that all of these proteins looked like they had been removed from aged stem cells. They injected an antibody to boost β1-integrin function into aged muscles to test whether this treatment would enhance muscle regeneration. Measurements of muscle fiber growth with and without boosting the function of β1-integrin showed that the protein led to as much as 50-percent more regeneration in cases of injury in aged mice.

When the same β1-integrin function-boosting strategy was applied to mice with muscular dystrophy, the muscle was able to increase strength by about 35 percent.

Fan said the team’s research will next try to determine what is happening inside the stem cells as they react with their immediate environment, as a step to understanding more about the interaction of the two. That, in turn, could help refine the application of integrin as a therapy for muscular dystrophy and other diseases, and for age-related muscle degeneration.

“We provide here a proof-of-principle study that may be broadly applicable to muscle diseases that involve [stem cell] niche dysfunction,” the authors wrote. “But further refinement is needed for this method to become a viable treatment.”

See the full article here .

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The Johns Hopkins University opened in 1876, with the inauguration of its first president, Daniel Coit Gilman. “What are we aiming at?” Gilman asked in his installation address. “The encouragement of research … and the advancement of individual scholars, who by their excellence will advance the sciences they pursue, and the society where they dwell.”

The mission laid out by Gilman remains the university’s mission today, summed up in a simple but powerful restatement of Gilman’s own words: “Knowledge for the world.”

What Gilman created was a research university, dedicated to advancing both students’ knowledge and the state of human knowledge through research and scholarship. Gilman believed that teaching and research are interdependent, that success in one depends on success in the other. A modern university, he believed, must do both well. The realization of Gilman’s philosophy at Johns Hopkins, and at other institutions that later attracted Johns Hopkins-trained scholars, revolutionized higher education in America, leading to the research university system as it exists today.