A new molecular mechanism found for stimulating hair growth

Findings may offer road map for next generation of therapies for androgenetic alopecia.

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Stem cells (SCs) are critically required for long-term tissue maintenance and regeneration. To perform their function, stem cells remain quiescent and transiently activate only when warranted, a tightly controlled switch.

A study team led by the University of California, Irvine has discovered how aging, or senescent, pigment-producing skin cells in nevi produce considerable hair growth. The finding might provide a blueprint for a new class of molecular treatments for androgenetic alopecia, a common hair loss in both men and women.

The study describes the key role of osteopontin and CD44 molecules in activating hair growth inside hairy skin nevi. These skin nevi accumulate large numbers of senescent pigment cells yet display very robust hair growth. Scientists discovered that senescent pigment cells release significant amounts of osteopontin. This signaling protein stimulates the stem cells of normally inactive and small hair follicles to grow long and thick hairs rapidly.

This research unequivocally demonstrates that cellular senescence has a positive side to it. Senescent cells are often seen as detrimental to regeneration and are assumed to promote aging as they amass in tissues throughout the body.

Stem cell activation effectively controls the growth of hair follicles; as these cells divide, hair follicles can cyclically create new hair. The stem cells in the follicle go into dormancy after each episode of hair development, remaining dormant until the next cycle starts.

The study used mice models of pigmented skin lesions with hyperactivated hair stem cells and rapid hair development, which closely matched the clinical findings reported in human hairy skin nevi. A more thorough examination of senescent pigment cells and the surrounding hair stem cells revealed that the former produced a signaling molecule called osteopontin in high levels, and the latter possessed a receptor molecule called CD44 in the hair stem cells. Osteopontin and CD44’s molecular connection triggered hair stem cells, resulting in strong hair growth.

Mouse models lacking osteopontin or CD44 were examined; they showed noticeably slower hair development, confirming the genes’ essential roles in the process. Human samples of hairy skin nevi have also been used to confirm the influence of osteopontin on hair growth.

First and co-corresponding author Xiaojie Wang, UCI associate specialist in developmental and cell biology, said, “Our findings provide qualitatively new insights into the relationship between senescent cells and tissue’s stem cells and reveal positive effects of senescent cells on hair follicle stem cells. As we learn more, that information can potentially be harnessed to develop new therapies that target properties of senescent cells and treat a wide range of regenerative disorders, including common hair loss.”

Journal Reference:

  1. Wang, X., Ramos, R., Phan, A.Q. et al. Signaling by senescent melanocytes hyperactivates hair growth. Nature 618, 808–817 (2023). DOI: 10.1038/s41586-023-06172-8
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