Battling baldness by jumpstarting stem cells with lactate
If stem cells can do everything from growing skulls to generating new heart tissue, you'd think they'd also be able to help regrow hair on balding heads. In fact, they soon might be able to do just that. Last year we saw that regular stem cells converted into epithelial stem cells (EpSCs) could be coaxed into growing new hair. Now, researchers out of UCLA have created a way to activate the stem cells already found in dormant hair follicles to get them doing their jobs again.
In the new study, the researchers discovered that the metabolic process that takes place in hair follicle stem cells is different from that which occurs in other skin cells. They found that these cells convert glucose into a molecule called pyruvate but this metabolite (product of metabolism) can take one of two paths. In can be sent to the power plant of a cell (known as mitochondria) and used as energy, or the cells can convert it to a different metabolite called lactate, the same substance that causes a burning sensation in muscles during exercise.
The researchers wondered if altering the chemical course of the glucose metabolites could change the behavior of inactive follicles.
"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, UCLA associate professor of biological chemistry and molecular and medical pharmacology.
To test things out, Christofk and co-study-lead William Lowry studied mice that had been genetically engineered to not produce lactate as well as those that had been altered to increase lactate production. They found that blocking lactate prevented hair follicle stem cells from being activated, while increasing lactate upped the production of hair.
"Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells," said Lowry, a professor of molecular, cell and developmental biology at UCLA. "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."
In the pursuit of those drugs, Lowry, Christofk and their team found two that could get the job done in different ways.
The first is called RCGD423 and it works by opening up an information highway of sorts between the outside of a cell and its nucleus through a pathway known as JAK-Stat. Building this highway increases lactate production and therefore turns the follicular stem cells to an active state, leading to increased hair growth.
The other drug is called UK5099. It keeps pyruvate from entering into the cells' mitochondria, forcing them to produce lactate instead and sparking accelerated growth.
Thus far, the two drugs have not yet been tested on humans, but if the rodent experiments are any indication, the medications could hold promise in reversing alopecia, hair loss caused by things like stress, hormone imbalances or plain old aging.
"Through this study, we gained a lot of interesting insight into new ways to activate stem cells," said Aimee Flores, a predoctoral trainee in Lowry's lab and first author of the study. "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."
The research has been published in the journal Nature Cell Biology.