Fat Cells Used to Heal Wounds

By Jane Farrell

Doctors have found a way to help wounds heal as regenerated skin rather than scar tissue. The method involves transforming the most common type of cells found in wounds into fat cells – something that was previously thought to be impossible in humans.

Researchers began this work at the Perelman School of Medicine at the University of Pennsylvania, which led to a large-scale, multi-year study in connection with the Plikus Laboratory for Developmental and Regenerative Biology at the University of California, Irvine. They published their findings online in the journal Science.

Fat cells called adipocytes are normally found in the skin, but they’re lost when wounds heal as scars. The most common cells found in healing wounds are myofibroblasts, which were thought to only form a scar. Scar tissue also does not have any hair follicles associated with it, which is another factor that gives it an abnormal appearance from the rest of the skin. Researchers used these characteristics as the basis for their work – changing the already present myofibroblasts into fat cells that do not cause scarring.

“Essentially, we can manipulate wound healing so that it leads to skin regeneration rather than scarring,” said George Cotsarelis, MD, the chair of the Department of Dermatology and the Milton Bixler Hartzell Professor of Dermatology at Penn, and the principal investigator of the project. “The secret is to regenerate hair follicles first. After that, the fat will regenerate in response to the signals from those follicles.”

According to a news release from the university, the study showed hair and fat develop separately but not independently. Hair follicles form first, and the Cotsarelis lab previously discovered factors necessary for their formation. Now they’ve discovered additional factors actually produced by the regenerating hair follicle to convert the surrounding myofibroblasts to regenerate as fat instead of forming a scar. That fat will not form without the new hairs, but once it does, the new cells are indistinguishable from the pre-existing fat cells, giving the healed wound a natural look instead of leaving a scar.

As they examined the question of what was sending the signal from the hair to the fat cells, researchers identified a factor called Bone Morphogenetic Protein (BMP). It instructs the myofibroblasts to become fat. This signaling was groundbreaking on its own, as it changed what was previously known about myofibroblasts.

“Typically, myofibroblasts were thought to be incapable of becoming a different type of cell,” Cotsarelis said. “But our work shows we have the ability to influence these cells, and that they can be efficiently and stably converted into adipocytes.” This was shown in both the mouse and in human keloid cells grown in culture.

“The findings show we have a window of opportunity after wounding to influence the tissue to regenerate rather than scar,” said the study’s lead author Maksim Plikus, PhD, an assistant professor of Developmental and Cell Biology at the University of California, Irvine. Plikus began this research as a postdoctoral fellow in the Cotsarelis Laboratory at Penn, and the two institutions have continued to collaborate.