Hair follicle stem cells contribute to wound healing

Wound at different stages of healing (A-C). The blue lines represent "clones" of cells originating from hair follicle stem cells. As the wound heals, the hair-follicle-derived cells migrate linearly toward the center of the wound in an apparent effort to heal the wound as quickly as possible. A, two days after wound. (Credit: George Cotsarelis, University of Pennsylvania School of Medicine; Nature Medicine). Click here for a high resolution image.

(Philadelphia, PA) -Hair follicle stem cells are important contributors to the wound-healing process, according to new research by investigators at the University of Pennsylvania School of Medicine. Using an animal model, the researchers discovered that stem cells in the hair follicle are enlisted to help heal wounds in the skin. This finding, published online in Nature Medicine last week, may suggest a therapeutic target for the development of drugs to encourage and promote wound healing.

B, five days after wound; blue streaks indicate that clones move inward. (Credit: George Cotsarelis, University of Pennsylvania School of Medicine; Nature Medicine). Click here for a high resolution image.

Wounds, including skin ulcers and other dermatological problems associated with diabetes, circulatory problems, and other diseases, are a growing medical problem in the United States, notes senior author George Cotsarelis, MD, Associate Professor of Dermatology. Previous work by the Penn research team had outlined the hair-growth process to show that stem cells in the hair follicle "bulge" area generate new lower hair follicles, which in turn, generate new hair. Their latest finding-that these same stem cells play a key role in initiating wound healing-will help lay the foundation for designing more effective wound-healing strategies.

Even minor wounding resulted in mobilization of follicle stem cells to generate daughter cells that quickly move into the wound area. "About one-third of the coverage of the wound came from the stem cells in the hair follicle," says Cotsarelis. "In the future, we think that we will be able to design treatments that enhance the flow of cells from the hair follicle to the epidermis in the hope of enhancing wound healing and treating patients with wounds."

Follow the Blue Light

Clinicians have known for some time that when the skin is abraded new cells come from the hair follicle. What remained a mystery was the exact nature of the origins of the new cells-specifically, what percentage stems from the deep follicle and what percentage from the epidermis near the wound.

Cotsarelis' team found that adult stem cells from the lowest portion of the hair follicle, or "bulge," quickly ascend the follicle in response to wounding and ultimately comprise about 30 percent of the new cells in a wound when it first starts to heal. In addition, the stem cells respond rapidly to surface wounding-within two days-by generating short-lived "transient-amplifying" cells that respond to acute wound-healing needs.

Using a genetically engineered mouse designed in their lab, the researchers were able to visually follow the fate of the stem cells as they migrated from deep within the skin to the surface wound site. The mouse stem cells express a reporter gene that encodes an enzyme, which can be detected with a special blue-color reaction. "We could see blue lines coming from the follicles going toward the center of the wound," says Cotsarelis. "They formed a striking radial pattern like the spokes of a wheel."

Hope for Hair Loss?

C, eights days after wound, the epidermis has completely closed. (Credit: George Cotsarelis, University of Pennsylvania School of Medicine; Nature Medicine). Click here for a high resolution image.

The research also showed that stem cells might be a therapeutic target in certain types of hair loss. Using a different engineered mouse also designed in the Cotsarelis lab, one in which the hair-follicle stem cells could be destroyed after administration of a drug, the researchers discovered that the animals permanently lost all of their hair. This hair loss mimics types of hair loss seen in humans called scarring alopecias. But, cautions Cotsarelis, more studies are needed to determine if the loss of hair-follicle stem cells plays a role in hair loss in humans.

This research was funded in part by the National Institutes of Health. Other co-authors in addition to Cotsarelis are Mayumi Ito, Yaping Liu, Zaixin Yang, Jennifer Nguyen, and Fan Liang, all from Penn, as well as Rebecca J. Morris from the Columbia University College of Physicians and Surgeons, New York. This

release and related images can also be found at: www.uphs.upenn.edu/news.

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