Self-policing stem cells diminish muscle scarring and fibrosis

Scientists at the Stanford University School of Medicine (CA, USA) have discovered a stem cell mechanism to reduce muscle scarring and fibrosis, which may help the development of therapies for conditions such as muscular dystrophy.

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Dec 09, 2016
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Scientists at the Stanford University School of Medicine (CA, USA) have found that treating mice with a compound that promotes expression of an inactive protein helps them heal from injuries with less scarring. This finding has potential in the field of degenerative diseases such as muscular dystrophy as well as normal aging.

Researchers led by Alisa Mueller, MD, PhD and Thomas Rando, MD, PhD, a professor of neurology and neurological sciences at Stanford, were investigating the protein PDGFRa, a transmembrane protein that sits on the surface of fibroadipogenic progenitors (FAPs) and is involved in the pathway activating FAP proliferation. FAPs are the muscle-embedded stem cells that produce the connective tissue framework that supports muscle development and regeneration, and must be appropriately regulated to repair injury, but not over-proliferate and cause fibrosis, making the muscle unable to contract and relax properly.

The team discovered that FAPs can adapt the length and activity of PDGFRa to allow them to respond most appropriately to aging, disease or injury. A full-length, active version of PDGFRa can be produced that responds to external signals to divide, while a short, inactive version of the protein can also be produced, which attenuates the growth signals by binding the factors but not transmitting the signal into the cell, preventing an over-response that can lead to scarring or fibrosis.

“We’ve found that the cells actively regulate the production of the inhibitory form of the protein, which is very surprising,” revealed Rando. “If they make less, the degree of fibrosis increases; if they make more, it decreases.”

The team used vivo-morpholino (a small molecule) that can bind and block access to small sections of mRNA to see if they could modify expression of the short, inhibitory version of the PDGFRa protein in a mouse model. Increasing the expression of the inhibitory version improved recovery from injury with less fibrosis and scarring in both young and old mice, whereas decreasing expression resulted in greater fibrosis.

“We’d like to test this approach in a mouse model of muscular dystrophy next,” continued Rando. “Interestingly, the vivo-morpholino we used is similar to a small oligonucleotide therapy currently being tested in clinical trials to stimulate the production of proteins missing in patients with Duchenne muscular dystrophy. Perhaps we could also use this approach to reduce fibrosis in this disease.”

Source: https://med.stanford.edu/news/all-news/2016/11/stem-cells-police-themselves-to-reduce-scarring-study-finds.html

Go to the profile of Freya Leask

Freya Leask

Publisher, Future Science Group

I am the Editor of RegMedNet, here to help users make the most of the website. I am passionate about digital and STM publishing, as well as regenerative medicine and medical 3D printing. Please get in touch if you have any queries or comments!

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