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Reactivating Stem Cells Regrows Hair

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Researchers at UCLA have offered new hope to people losing their hair. These scientists have discovered a way to activate stem cells in the follicles to make hair grow again.

The new study published in the journal Nature Cell Biology gives us a tantalizing look into how we can restore hair growth and treat conditions such as baldness and alopecia [1]. These conditions are associated with hormonal imbalance, stress, aging, and chemotherapy treatment.

So what are hair follicle stem cells?

Hair follicle stem cells are long-lived cells that reside in the hair follicles in the skin. These hair-producing cells are normally quiescent (dormant) between hair growth cycles.

Various factors regulate stem cell quiescence, and, in extreme cases, they fail to activate, causing hair loss.

The research

The researchers in this study discovered that the metabolism of hair follicle stem cells is different from other types of cells in the skin. Cells break down nutrients needed for cell division and produce energy for various cellular functions. This process involves enzymes that change nutrients into metabolites, intermediates and byproducts of metabolism.

As hair follicle stem cells take in glucose, they convert it into a metabolite called pyruvate. The cell can use pyruvate for its mitochondria, the power plants of the cell, or it can convert this into yet another metabolite known as lactate.



The researchers wanted to find out if reducing the supply of pyruvate to the mitochondria could make the stem cells more active and induce hair growth by forcing them to create more lactate.

To test this, the team first genetically inhibited the production of lactate in mice and found that this prevented the activation of hair follicle stem cells. They then increased the production of lactate in mice and saw that hair growth was accelerated due to increased hair follicle stem cell activation.

Two drugs were tested

Having discovered this, they then began to search for drugs that could be applied topically to the skin and have the same effect.

The first drug they found was RCGD423, a compound that activates the JAK-Stat pathway, which transmits information from outside the cell to the nucleus and is a critical communication path. The researchers demonstrated that JAK-Stat activation increases lactate production and induces hair follicle stem cell activation, which results in faster hair growth.

The second drug, UK5099, prevents pyruvate from entering the mitochondria, thus forcing the production of lactate and, again, resulting in activation of hair follicle stem cells and more rapid hair growth.

Conclusion

While the therapy is still in its early days, it is promising news for people suffering from baldness or alopecia.

At first glance, it might not be immediately obvious how this relates to aging, but it very much does. This and other research shows that stem cells can be brought back from dormancy to improve tissue function.

This suggests that we may find other, similar, ways to manipulate in situ stem cell populations in other tissues in order to activate them and increase tissue regeneration in order to treat other age-related diseases.



Literature

[1] Aimee Flores, John Schell, Abigail S. Krall, David Jelinek, Matilde Miranda, Melina Grigorian, Daniel Braas, Andrew C. White, Jessica L. Zhou, Nicholas A. Graham, Thomas Graeber, Pankaj Seth, Denis Evseenko, Hilary A. Coller, Jared Rutter, Heather R. Christofk & William E. Lowry Lactate dehydrogenase activity drives hair follicle stem cell activation Nature Cell Biology (2017) doi:10.1038/ncb3575

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