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Step away from the aspirin? Inflammatory molecule boosts muscle regeneration, say Stanford scientists

My gym routine has been suffering lately. So I felt a pang of guilt writing my most recent release about muscle soreness after exercise or trauma. It's been a while since I've felt that particular stiffness and pain that follows a productive workout.

Like many others, however, I do remember sometimes reaching for a dose of painkillers like aspirin or ibuprofen to combat the temporary discomfort. But a recent study led by Stanford microbiologist and immunologist Helen Blau, PhD, suggests that, at least in laboratory mice, these anti-inflammatory drugs may actually inhibit muscle regeneration.

Together with senior scientist Andrew Ho, PhD, and postdoctoral scholar Adelaida Palla, PhD, Blau found that a naturally occurring spike in an inflammatory molecule called prostaglandin E2 after injury kicks muscle stem cells into action like a bossy drill sergeant. The researchers published their findings today in the Proceedings of the National Academy of Sciences.

As I describe in our press release today:

Muscle stem cells usually nestle quietly along the muscle fibers. They spring into action when a muscle is damaged by trauma or overuse, dividing rapidly to generate enough muscle cells to repair the injury. But it’s not entirely clear what signals present in inflammation activate the stem cells.

Prostaglandin E2, or PGE2, is a metabolite produced by immune cells that infiltrate the muscle fiber as well by the muscle tissue itself in response to injury. Anti-inflammatory treatments have been shown to adversely affect muscle recovery, but because they affect many different pathways, it’s been tough to identify who the real players are in muscle regeneration.

Ho, Palla and Blau found that treating the animals with a single dose of prostaglandin E2 after injury helped them regenerate their muscles and regain muscle strength more efficiently. Conversely, blocking the inflammatory process with non-steroidal anti-inflammatory drugs inhibited regeneration and impaired their ability to regain their strength.

The researchers next plan to try to reproduce these results in human muscle stem cells. They are particularly excited about the finding because prostaglandin E2 is already approved for use in humans to help induce labor in pregnant women. They envision the possibility of using the molecule to enhance muscles' natural regenerative capacity without having to remove and tinker with the muscle stem cells themselves.

As Blau, who directs Stanford’s Baxter Laboratory for Stem Cell Biology, told me:

Our goal has always been to find regulators of human muscle stem cells that can be useful in regenerative medicine. It might be possible to repurpose this already FDA-approved drug for use in muscle. This could be a novel way to target existing stem cells in their native environment to help people with muscle injury or trauma, or even to combat natural aging.

Previously: Elderly muscle stem cells from mice rejuvenated by Stanford scientists, "Home away from home": Artificial muscle fibers keep lab-grown stem cells happy and Stem cells implicated in Duchenne muscular dystrophy
Photo by PublicDomainPictures

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