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January 08, 2017

Penn dermatologists discover unlikely source to prevent scarring in wounds

Researchers at the University of Pennsylvania's Perelman School of Medicine have broken ground on a promising new treatment method that could vastly improve the way our wounds heal and minimize the appearance of visible scars.

As scientists continue to explore the most feasible applications of regenerative medicine, a research team at Penn, joined by partners from the Pikus Laboratory for Developmental and Regenerative Biology at the University of California, Irvine, have turned to fat cells as an organic building block for recovery.

When the body responds to a nasty cut or laceration, its natural response is to initiate healing with myofibroblasts, a cell type that secretes a smooth muscle protein and contracts the injury site to form a scar. Since this repair process does not generate any hair follicles, scar tissue forms with an appearance that stands out from the rest of the skin.

While these myofibroblasts aid in the development of a scar, the wound site simultaneously loses fat cells known as adipocytes, which normally help maintain the uniform appearance of the skin. By advancing previous findings on the biological factors involved in hair follicle formation, the Penn and U.C., Irvine researchers demonstrated that myofibroblasts can be instructed to turn into fat cells, a process previously thought to be impossible in human beings.

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

Cotsarelis' team previously knew that hair follicles form first before fat cells and that a specific set of factors are necessary for the formation of these follicles. What the latest study reveals is that while hair and fat develop separately, they don't form independently of one another.

By identifying additional factors produced during hair follicle regeneration — specifically Bone Morphogenic Protein (BMP) — researchers determined that these follicles can be used to direct myofibroblasts surrounding a wound to regenerate as fat instead of forming a scar. Even though the hair forms first, the new fat cells that eventually form are indistinguishable from those prior to an injury. The resulting wound heals with a natural appearance rather than a scar, as demonstrated in both mice and human keloid cells grown in culture.

"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. It’s highly desirable from a clinical standpoint, but right now it’s an unmet need."

Researchers believe that increasing fat cells in human tissue could have implications broader than cosmetic improvements in healing wounds. Loss of fat cells frequently occurs in a range of conditions and treatments, HIV among them, and also occurs naturally as part of the aging process that results in permanent wrinkling in the face.

“Our findings can potentially move us toward a new strategy to regenerate adipocytes in wrinkled skin, which could lead us to brand new anti-aging treatments,” Cotsarelis said.

As a next step, Costarelis' lab will focus on mechanisms that promote skin and hair follicle regeneration, while the U.C., Irvine lab will examine other aspects of cell reprogramming in skin wounds.

The research from Penn and U.C., Irvine, funded by by the National Institutes of Health and the Edward and Fannie Gray Hall Center for Human Appearance, was published last week in the journal "Science."

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