All skin wounds, whether caused by injury or surgery, eventually leave a scar. Some scars are so small they’re nearly invisible, but many scars are large and ungainly and can even affect the function of the body part where they’re located. Researchers at the University of Pennsylvania’s (UPenn) Perelman School of Medicine, in collaboration with the Plikus Laboratory for Developmental and Regenerative Biology at the University of California, Irvine, have pioneered a method to regenerate the skin after a wound without resulting in any scar tissue, leaving it looking just like unscarred skin. Their results were published recently in the journal Science.
When skin suffers a wound, it loses fat cells called adipocytes, as well as hair follicles and sweat glands. Wounded skin also produces cells known as myofibroblasts, which researchers believed existed primarily to produce the collagen that creates the scar. “Those cells were thought to be a dead end, either they died off, or just turned into a big scar,” George Cotsarelis, co-author of the paper and professor and chair of the dermatology department at UPenn, tells mental_floss.
However, when they studied these cells in mouse models, they found that when myofibroblasts are placed near hair follicle cells, they transform into fat cells, smoothing out the skin, rather than producing a scar. “We were very surprised to see they had the ability to also turn into fat, and that the follicle was instructing them to do so,” Cotsarelis says. There was no fat in any cells that didn’t have follicles.
“Our second part was to figure out how the follicle was talking to the myofibroblast,” he says. They soon isolated the signaling pathway by which the follicle “spoke” to the myofibroblast: bone morphogenic protein (BMP), a protein the follicle secreted that told the myofibroblast to turn into fat.
After applying BMP to induced wounds in genetically modified mice, the wound sites regenerated into smooth, normal, unscarred skin. This result was so promising, they then collected cells from human keloid scars—scars that are large and raised—and cultured them in petri dishes. “We grew those [human] fibroblast keloid cells in a culture and added in BMP and differentiation media that promotes fat,” he says. The BMP successfully converted the keloid scar cells into fat, which “was very unexpected and kind of remarkable.…The fact that human cells turned into fat cells was really exciting, because often you don’t know if mouse studies will translate into human."
Cotsarelis anticipates beginning human trials within a year, since BMP is already used in clinical applications. If the technology holds up in human trials as well as it did for in vivo human cells, Cotsarelis is optimistic that it might offer new kinds of treatment for all scars, but especially keloid scars, for which current treatments “are very poor,” he says. When keloids are cut out, they often "just regrow to bigger than they were before,” he says. Cortisone can occasionally flatten and soften them, but ultimately, once you have one, you always have one.
He is hopeful that by using BMP in keloids, “we can get them to turn into fat, which would provide a much better cosmetic outcome.” He says this will be especially helpful in the case of surgeries to the face. “Scars in general are cosmetic problems, but they can affect function depending on where they are, and they can cause problems emotionally as well, regarding appearance,” he says.
The research might also open doors of inquiry to study scarring that affects organs such as the liver and the lungs in certain diseases, and may offer ways to regenerate fat in aging skin to smooth out the appearance of wrinkles.