The results appear online on January 22 in the journal Science Advances.
"Lots of processes are taking place throughout the human body during exercise, and it is difficult to tease apart which systems and cells are doing what inside an active person," said Nenad Bursac, professor of biomedical engineering at Duke. "Our engineered muscle platform is modular, meaning we can mix and match various types of cells and tissue components if we want to. But in this case, we discovered that the muscle cells were capable of taking anti-inflammatory actions all on their own."
Inflammation is not inherently good or bad. When the body is injured, an initial low-level inflammation response clears away debris and helps tissue rebuild. Other times, the immune system overreacts and creates an inflammatory response that causes damage, like the often deadly cytokine storms brought on by some cases of COVID-19. And then, there are diseases that lead to chronic inflammation, such as rheumatoid arthritis and sarcopenia, which can cause muscle to waste away and weaken its ability to contract.
Among many molecules that can cause inflammation, one pro-inflammatory molecule in particular, interferon gamma, has been associated with various types of muscle wasting and dysfunction. While previous research in humans and animals has shown that exercise can help mitigate the effects of inflammation in general, it has been difficult to distinguish what role the muscle cells themselves might play, let alone how they interact with specific offending molecules, such as interferon gamma.
"We know that chronic inflammatory diseases induce muscle atrophy, but we wanted to see if the same thing would happen to our engineered human muscles grown in a Petri dish," said Zhaowei Chen, a postdoctoral researcher in Bursac's laboratory and first author of the paper. "Not only did we confirm that interferon gamma primarily works through a specific signaling pathway, we showed that exercising muscle cells can directly counter this pro-inflammatory signaling independent of the presence of other cell types or tissues."
