Stem cell activation may be a new therapeutic avenue for baldness or alopecia, in which hair is lost because of aging, chemotherapy, stress or hormonal imbalances. Researchers at UCLA have developed a method to stimulate such cells in hair follicles, finding that it causes hair growth. This work is outlined in the video below and had been reported in Nature Cell Biology.
Hair follicles contain stem cells, which are normally inactive or quiescent. But when a new hair cycle starts and hair growth begins, the stem cell in the follicle becomes active. Many factors influence that activation of stem cells. When the activation fails, hair loss occurs.
Researchers Heather Christofk and William Lowry of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA determined that the stem cells of hair follicles have a different metabolism than other skin cells. As cells consume materials they require for energy, nutrients are broken down by enzymes and metabolites are produced. When hair follicle stem cells metabolize glucose, one such metabolite is pyruvate. The pyruvate is then either sent to the cell’s mitochondria, or the pyruvate can be broken down further into lactate.
“Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate and if that would activate the cells and grow hair more quickly,” said Christofk, an Associate Professor of Biological Chemistry and Molecular and Medical Pharmacology.
When the investigators turned to a mouse model and halted lactate production through genetic engineering, stem cells in hair follicles did not activate. Further studies with collaborators in the Rutter lab at the University of Utah indicated that when lactate production was genetically promoted in mice, hair follicle activation was accelerated and the hair cycle increased.
“Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells,” noted Lowry, a Professor of Molecular, Cell and Developmental Biology. “Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.”
Two drugs were found that were able to stimulate lactate production in the skin of mice. The drugs worked in different ways. One, RCGD423, activated a pathway in cells called JAK-Stat; the subsequently increased lactate production drove cell activation and hair growth. The other drug, UK5099, stops pyruvate from going to the mitochondria. That forces lactate production in hair follicle stem cells and in mice, hair growth accelerates. These drugs have unfortunately not yet been tested in people.
“Through this study, we gained a lot of interesting insight into new ways to activate stem cells,” said first author Aimee Flores, a predoctoral fellow in the Lowry lab. “The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think we’ve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; I’m looking forward to the potential application of these new findings for hair loss and beyond.”