In a discovery that could lead to new treatments for individuals who have hair and scalp disorders, a team of researchers have honed in on the growth factor responsible for helping hair follicles form and regenerate during the wound-healing process.

When Fgf9 was overexpressed in a mouse model, there was a two- to three-fold increase in the number of new hair follicles produced, according to researchers from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

The hope is that this growth factor could be used therapeutically for people with various hair and scalp disorders.

The findings appear in an advance online publication of Nature Medicine.



“The findings help explain why humans don’t regenerate their hair after wounding,” says senior author George Cotsarelis, MD, professor and chair of Dermatology the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, in a news release. “The study also points us to a way to treat wounds and grow hair.”

Following up on earlier work, which showed that increased signaling from the Wnt pathway doubled the number of new hair follicles, researchers looked further upstream in the pathway and identified an important cascade of signals that prompt further expression and perpetuate and amplify signals sent during a crucial phase of hair-follicle regeneration.

Fgf9 is initially secreted from gamma delta T cells, a rare subset of T cells involved in the immune response. Once released, Fgf9 serves as the catalyst for a signal sent via the dermal Wnt pathway. The signal prompts further expression of Fgf9 in fibroblasts, and adds to the generation of new hair follicles.

When a wound occurs in an adult person, hair follicle growth is blocked and the skin heals with a scar. However, hair does regenerate to a great extent in the wound-healing process in mice. The team compared how the process works in adult mice to humans.

Humans have low numbers of gamma delta T cells in their skin compared to mice, and this may explain why human skin scars but does not regenerate hair follicles.

In adult mice, the amount of Fgf9 secreted modulates hair-follicle regeneration after wounding. When Fgf9 was reduced, there was a decrease in wound-induced hair-follicle growth.

By contrast, when Fgf9 was increased, there was a two- to three-fold increase in the number of new hair follicles, equal to the amount seen in the mice expressing Wnt. Importantly, when the investigators added Fgf9 back to the wounds that do not normally regenerate, FGF9 triggered the molecular cascade of events necessary for skin and hair regeneration; thus, leaving the door open for using Fgf9 to treat wounds and hair loss in people.

Treatments intended to compensate for the lack of Fgf9 may be most effective if timed with a wounding response. “Testing activators of Fgf9 or Wnt pathways during the wound-healing process may be warranted,” they suggest.