Fat and hairy skin doesn’t form scars

Our body’s ability to heal after a cut is an amazing, but it often leaves behind an unsightly scar. Now, researchers have found a way to prevent scarring by changing scar cells to fat cells.

Every scar tells a tale, and the bigger the scar, the more exciting the story. However, scars from major injuries, surgery, or severe burns can be life-altering by drastically changing our appearance or even inhibiting movement. Although some organisms, such as zebrafish or salamanders, can regenerate lost fins or tails, mammals heal cuts with scar tissue—a functionally different skin replacement that doesn’t have fat or hair. Now, an unexpected discovery published in Science shows how converting myofibroblast cells into fat cells can prevent scarring (1).

Most research concerning scar-prevention focuses on inducing hair growth or minimizing the number of myofibroblasts in a wound. In 2007, George Cotsarelis and his team at the University of Pennsylvania discovered an unusual case of naturally occurring hair re-growth in the center of large wounds in mice (2). Following this discovery, Maksim Plikus from the University of California Irvine, who led this study in collaboration with Cotsarelis, found new fat cells (adipocytes) exclusively surrounding the new hair follicles. The combination of fat and hair created normal-looking skin in the center of large wounds.

Using several strains of transgenic mice, Plikus, Cotsarelis, and their teams determined that the new adipocytes came from myofibroblasts—cells previously thought to be differentiated and unable to convert into a new cell type. RNA-Seq analysis showed that wound-induced hair follicles triggered the bone morphogenetic protein (BMP) signaling pathway in myofibroblasts and converted them to adipocytes, an observation the team verified in knockout mice.

The researchers next treated human cells from keloid scars—benign growths resulting from excessive scar tissue build-up—in culture with BMP and successfully transformed the cells into adipocytes. Adding hair follicles to keloid scar cells induced adipocyte conversion, further indicating that hair follicles turn myofibroblasts into adipocytes through the BMP signaling pathway.

“This is sort of a fundamentally different approach to potential future scar removal therapies,” said Plikus, who plans to continue examining the signaling mechanism of myofibroblast conversion. Converting myofibroblasts to adipocytes provides a method to prevent scarring by regenerating normal skin that has fat and hair.

This work presents not only a potential new therapy for scars but also shows that the use of a single molecule can initiate cell-type conversion, an idea that may heavily influence wound-healing research. “I think it will open people’s eyes to the possibility for other cell transformations,” said Malcolm Maden from the University of Florida, who was not associated with this study. “Ultimately it may lead to the discovery of something else that could cut down on scarring.”