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Researchers Discover Immature Stem Cells in Hair Follicles

Dermatologists have made a groundbreaking discovery in their quest to unravel the mystery of what causes gray hair. It is now conceivable that one day, scientists could be able to reverse gray hair. According to a new study published in the journal Nature on April 19, 2023, melanocyte stem cells (McSC), residing in hair follicles, are responsible for pigmentation in hair and skin. The McSCs produce cells, which are essential for the production of hair pigment that ranges from black, brown, red, and blonde.

For melanocyte stem cells to produce pigment, they need to be at the bottom of the hair follicle, referred to as the germ, to produce the pigment. After that, the stem cells migrate back to the top of the hair follicle, called the bulge, where they revert to their immature state and prepare to repeat the process again.

The research has shown that when the melanocyte stem cells get stuck in the bulge, they remain immature and fail to produce enough new cells needed to produce pigment, which leads to the production of gray or white hair instead of a person’s natural hair color. To overcome this challenge, researchers must work to understand what causes McSC to move around, and if they can mobilize them to the hair germ compartment, they can participate in regenerating mature cells that can produce pigment.

Dr. Qi Sun, a postdoctoral researcher specializing in dermatology at NYU Langone Health in New York City, who led the study, explains that one ramification of their research could be to figure out how to mobilize stuck stem cells in the bulge to the hair germ compartment where they can regenerate mature cells that produce pigment.

Researchers already understand that melanocyte stem cells do not behave like most other stem cells, which mature until they die. For McSC, maturation is fluid, and they move back and forth between stages of maturation by moving around different compartments in hair follicles with different proteins that prompt McSC to be in different stages of maturity.

In the study, the researchers simulated the natural growth and shedding of human hair by strategically plucking hairs on mice and measuring differences between hairs that regenerated from plucked follicles and those produced by follicles that had not simulated shedding. They found that McSC appeared to tire sooner than other stem cells in the hair follicle. In plucked or “older” regrown hairs, 50 percent of McSC were stuck in the bulge, compared with 15 percent in the younger, unplucked hairs.

Natasha Mesinkovska, MD, PhD, an associate professor of dermatology and vice-chair for clinical research in dermatology at the University of California Irvine School of Medicine, who was not involved in the mice study, explains that the fact that McSCs get stuck in the bulge makes sense because the bulge is very immune-protected. In some diseases, the immune privilege is lost, leading to hair loss.

Dr. Mesinkovska notes that the new findings could help dermatologists better understand other hair conditions, not just graying. The authors of the study also noted that graying hair could be protective. The same stem cells involved in hair pigmentation, melanocytes, are also where melanoma, the deadliest form of skin cancer, forms. Therefore, if stem cell-related therapies are developed, they will need to strike a delicate balance between activating stem cells enough to reverse grays, but not so much that it causes unintended consequences.

Dr. Mesinkovska emphasizes the need for carefulness in the pursuit of making things last forever, stating that we do not want melanocytes to be super active forever. “There’s a reason you don’t let things divide uncontrollably forever.”