Integrins

Scientists find new stem cell target for regenerating aging muscles

/ Karen Ring / Leave a comment
Young Arnold (wiki)

Young Arnold (wiki)

Today I’m going to use our former governor Arnold Schwarzenegger as an example of what happens to our muscles when we age.

One of Arnold’s many talents when he was younger was being a professional bodybuilder. As you can see in this photo, Arnold worked hard to generate an impressive amount of muscle that landed him lead roles in movies Conan the Barbarian and The Terminator.

Older Arnold

Older Arnold

If you look at pictures of Arnold now (who is now 68), while still being an impressively large human being, it’s obvious that much of his muscular bulk has diminished. That’s because as humans age, so do their muscles.

Muscles shrink with age

As muscles age, they slowly lose mass and shrink (a condition called sarcopenia) because of a number of reasons – one of them being their inability to regenerate new muscle tissue efficiently. The adult stem cells responsible for muscle regeneration are called satellite cells. When muscles are injured, satellite cells are activated to divide and generate new muscle fibers that can repair injury and also improve muscle function.

However, satellite cells become less efficient at doing their job over time because of environmental and internal reasons, and scientists are looking for new targets that can restore and promote the regenerative abilities of muscle stem cells for human therapeutic applications.

A study published earlier this week in Nature Medicine, identified a potential new target that could boost muscle stem cell regeneration and improved muscle function in a mouse model of Duchenne muscular dystrophy.

β1-integrin is important for muscle regeneration

Scientists from the Carnegie Institute of Washington found that β1-integrin is important for maintaining the homeostasis (or balance) of the muscle stem cell environment. If β1-integrin is doing its job properly, muscle stem cells are able to go about their regular routine of being dormant, activating in response to injury, dividing to create new muscle tissue, and then going back to sleep.

When the scientists studied the function of β1-integrin in the muscles of aged mice, they found that the integrin wasn’t functioning properly. Without β1-integrin, mouse satellite cells spontaneously turned into muscle tissue and were unable to maintain their regenerative capacity following muscle injury.

Upon further inspection, they found that β1-integrin interacts with a growth factor called fibroblast growth factor 2 (Fgf2) and this relationship was essential for promoting muscle regeneration following injury. When β1-integrin function deteriorates as in the muscles of aged mice, the mice lose sensitivity to the regenerative capacity of Fgf2.

Restoring muscle function in mice with muscular dystrophy

By using an antibody to artificially activate β1-integrin function in the muscles of aged mice, they were able to restore Fgf2 responsiveness and boosted muscle regeneration after injury. When a similar technique was used in mice with Duchenne muscular dystrophy, they observed muscle regeneration and improved muscle function.

Muscle loss seen in muscular dystrophy mice (left). Treatment with beta1 intern boosts muscle regeneration in the same mice (right). (Nature Medicine)

Muscle loss seen in muscular dystrophy mice (left). Treatment with B1-integrin boosts muscle regeneration in the same mice (right). (Nature Medicine)

The authors believe that β1-integrin acts as a sensor of the muscle stem cell environment that it maintains a balance between a dormant and a regenerative stem cell state. They conclude in their publication:

“β1-integrin senses the SC [satellite cell] niche to maintain responsiveness to Fgf2, and this integrin represents a potential therapeutic target for pathological conditions of the muscle in which the stem cell niche is compromised.”

Co-author on the study Dr. Chen-Ming Fan also spoke to the clinical relevance of their findings in a piece by GenBio:

“Inefficient muscular healing in the elderly is a significant clinical problem and therapeutic approaches are much needed, especially given the aging population. Finding a way to target muscle stem cells could greatly improve muscle renewal in older individuals.”

Does this mean anyone can be a body builder?

So does this study mean that one day we can prevent muscle loss in the elderly and all be body builders like Arnold? I highly doubt that. It’s important to remember these are preclinical studies done in mouse models and much work needs to be done to test whether β1-integrin is an appropriate therapeutic target in humans.

However, I do think this study sheds new light on the inner workings of the muscle stem cell environment. Finding out more clues about how to promote the health and regenerative function of this environment will bring the field closer to generating new treatments for patients suffering from muscle wasting diseases like muscular dystrophy.

Meet the proteins that tell stem cells where to move and how

/ Kevin McCormack / Leave a comment

 

Protein word art

Word cloud art work which shows all the proteins identified by the researchers

The environment you grow up in can have a huge influence on how you turn out. That applies to people, and to stem cells too. Now a new study has identified 60 proteins that can have a big impact on how cells react to the world around them, and how they communicate with each other.

Just as it is easier for us to move across firm ground than it is to slosh our way through a soggy, muddy field, it’s easier for stem cells to move smoothly and quickly over a solid surface than over a soft, giving surface. This is particularly true for tumor cells, which move much faster on a hard surface than any other kind.

It’s not just speed that is affected by the kind of surface you place stem cells on. For example certain stem cells placed on a hard surface will specialize and turn into bone, whereas if you place those same cells on a very soft surface they will turn into nerve cells.

The problem is we didn’t know much about why that was the case, we didn’t understand the mechanism at play that caused those cells to behave that way.

Now we do.

A team at the University of Manchester in England tackled this problem by researching integrins; these are receptors that are responsible for cell-to-cell communication, cell growth and function. Integrins are typically found at the surfaces and edges of cells and provide proteins with a convenient place to hang out when they interact with the world around them.

The researchers looked at 2400 examples of these integrin-protein clusters and, using mass spectrometry, narrowed their search down to 60 proteins that they identified as being essential in linking information from the integrins to the rest of the cellular world.

The work was published in Nature Cell Biology. In an accompanying news release Dr. Jon Humphries, one of the lead researchers, talked about the significance of the work:

“Understanding how cells sense their environment is an important step in understanding how, for example, cancer cells move or how stem cells take on different jobs.”

His colleague, Professor Martin Humphries, says understanding how cells sense where they are and how to behave gives us new insights into how we can use that knowledge to better control their movement:

“Our findings on how cells sense their environment have unlocked an important key to understanding how we can persuade cells to form different tissues and how we might stop cell movement in diseases such as cancer.”