Stem cells have a neat trick to prevent tissue scarring

A CIRM-funded study from the Stanford University School of Medicine has discovered that stem cells in muscle tissue “police themselves” to reduce fibrosis or the buildup of scar tissue. The ability to prevent scarring could promote anti-aging properties by keeping muscles healthy and functional and could also benefit patients with muscle wasting diseases like muscular dystrophy. The study appeared in the journal Nature earlier this week.

The Stanford team, led by Professor Thomas Rando, was interested in understanding how healthy muscle tissue regenerates under normal conditions and in response to injury. They focused on cells called fibro-adipogenic progenitors (FAPs), which live in the muscle and produce a framework of connective tissue that promotes muscle regeneration.

By studying FAPs in mice, the scientists found that these cells produced a protein called platelet-derived growth factor receptor alpha (PDGFRa), which regulates their ability to proliferate, or make more copies of themselves. FAPs produce different versions of PDGFRa as a way to police themselves and deal with injury and disease.

The normal version of PDGFRa tells FAPs to divide and proliferate. Typically, this response is a good thing if FAPs are trying to repair tissue damage, but too much cell proliferation can lead to fibrosis and scarring. To counteract this, FAPs can produce a truncated version of PDGFRa, which tells FAPs to stop dividing and prevents tissue scarring.

Senior author on the study, Professor Thomas Rando, explained in a Stanford Medicine news release why it’s important to prevent scarring in muscle tissue:

Dr. Thomas Rando, Stanford

Dr. Thomas Rando, Stanford

“Fibrosis occurs in many degenerative diseases and also in normal aging. It negatively impacts muscle regeneration by altering the stem cell niche and inhibiting the stem cell function. In addition, as more scarring occurs, muscles become stiff and can’t contract and relax smoothly.”

 

Knowing that the truncated version of PDGFRa can stop FAPs from proliferating too much and cause scarring, the team found a way to force FAPs to generate this shortened version of PDGFRa in mice. When they tried this approach in mice, they observed that both young and old mice produced less scarring after healing from muscle injury. On the other hand, if these mice produced less of the truncated PDGFRa, the mice had more scarring than they normally would.

Nature.

Muscle tissue in old mice shows signs of scarring (left) while old mice treated with the truncated PDGFRa have reduced scarring in their muscle (right). (Nature)

Rando’s team believes that they can harness the properties of self-policing stem cells like FAPs to develop new potential therapies that can treat fibrotic diseases. In future studies, Rando hopes to apply their approach to treating muscular dystrophy – a muscle wasting disease that also is associated with increased fibrosis.

“We’d like to test this approach in a mouse model of muscular dystrophy next. Perhaps we could also use this approach to reduce fibrosis in this disease.”

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