UCLA researchers have discovered a new way to activate the stem cells in the hair follicle to make hair grow. The research may lead to new drugs that could promote hair growth for people with baldness or alopecia, which is hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy. Hair follicle stem cells are long-lived cells in the hair follicle that are present in the skin and produce hair throughout a person’s lifetime. They are quiescent, meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases, they fail to activate, which is what causes hair loss.
The study by Heather Christofk, PhD, and William Lowry, PhD, both of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, found that hair follicle stem cell metabolism is different from other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce metabolites. As hair follicle stem cells consume the nutrient glucose — a form of sugar — from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can send pyruvate to their mitochondria — the part of the cell that creates energy — or convert pyruvate into another metabolite called lactate.
The research team first blocked the production of lactate genetically in mice and showed that this prevented hair follicle stem cell activation. Conversely, in collaboration with the Rutter lab at the University of Utah, they increased lactate production genetically in the mice, which accelerated hair follicle stem cell activation, increasing the hair cycle.
The team identified two drugs that, when applied to the skin of mice, influenced hair follicle stem cells in distinct ways to promote lactate production. The first drug, called RCGD423, activates a cellular signaling pathway called JAK-Stat, which transmits information from outside the cell to the nucleus of the cell. The research showed that JAK-Stat activation leads to the increased production of lactate, and this in turn drives hair follicle stem cell activation and quicker hair growth. The other drug, called UK5099, blocks pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice.
“Lactate Dehydrogenase Activity Drives Hair Follicle Stem Cell Activation,” Nature Cell Biology, August 14, 2017