Penn Medicine researchers unveiled in a recently published paper that a type of stem cell originating in skeletal muscle cells can turn into bone.
Published in the Proceedings of the National Academy of Sciences, the study was led by Ling Qin, a professor of Orthopaedic Surgery at Penn Med, and Jaimo Anh, former Penn Med researcher and current professor of Orthopaedics at Emory University. The discovery could dramatically improve bone healing following catastrophic fractures.
In an interview with The Daily Pennsylvanian, Qin noted that her lab has had a “long-term interest” in fracture healing, specifically regarding muscles near the bone.
The healing of fractured bone has widely been held to be mainly done by periosteum progenitor cells, which are part of the membrane covering all bones in the body. However, this has limited efficacy, especially regarding “open fracture” cases that involve a significant loss of soft tissue due to bone breaking the skin, for reasons unclear to scientists.
Most treatments currently in clinical practice only focus on healing bone tissue itself within fractures, but this research by Qin, Ahn, and their colleagues may help increase focus on the muscles next to bones as crucial sites for injury healing.
“No one pays attention to the muscle near the bone, but in clinics, clinicians have known for a long time that if [patients] have a big bone defect, they could put a muscle flap on top of it to help healing, though they don't know the mechanism,” Qin said.
Her lab decided to utilize a technique known as lineage tracing to determine this mechanism. They used this method to trace Prg4+ stem cells — which originate in muscles that support the skeleton — in vivo and track where they went in mouse models that present with bone fractures.
This process led them to discover that Prg4+ was a special type of stem cell known as fibro-adipogenic progenitor stem cells.
The researchers also found that Prg4+ acted by migrating to the fracture site within the body, where it then increased the production of cells necessary to repair a bone in between the bone calluses — the temporary structure formed on the bone to guide healing — and skeletal muscle. The role of Prg4+ in this process was found to be significant, as purposeful destruction of Prg4+ cells by the researchers led to slower healing and repair times.
More surprisingly, they saw that following the healing of the bone, cells that originally were Prg4+ cells had become bone cells that could give rise to periosteum stem cells for healing in case of any future possible fractures. This indicated that stem cells could transform from muscle to bone.
“This could have a real impact in areas where muscles are simply just not as prevalent, like the knee and ankle,” Ahn told Penn Today. “There’s also potentially a significant impact on older adults whose muscle mass diminishes naturally, and healing doesn’t occur like it once did.”
Qin echoed these remarks, noting an application of this research with personal relevance for her and other women going through menopause, which places them at greater risk for osteoporosis.
“One important feature of osteoporosis is that very likely I will get a fracture some time later. For a woman [with osteoporosis] greater than 55 years old, at least half of them will eventually get a fracture during the rest of their life,” Qin said. "Those kinds of fractures in old people are difficult to heal. So this [research] is also helping me in the future. Maybe if I have a fracture then, I could have a better treatment to get that bone healed.”
