"The groundwork of all happiness is health." - Leigh Hunt

Could “stuck” stem cells be in charge?

April 20, 2023 – Your hair has stem cells near the hair roots which might be vital for making your hair brown, black, or one other natural color. But these cells must migrate to a different a part of the follicle and alter to create hair color. When these special stem cells get “stuck” and might now not do their job, gray hair comes out as a substitute, recent research shows.

These cells, called melanocyte stem cells (McSCs), must mature into melanocytes, or pigment cells. They can survive for years, but die prior to other nearby cells, reminiscent of hair follicle stem cells. This difference may explain why people go gray but still grow hair.

A brand new finding is that these cells can move throughout the hair follicle without losing their “stemness.” Similar to recycling, they begin as “undifferentiated” stem cells, move and mature to perform their job of coloring hair, after which transform back into more primitive stem cells.

Traditionally, it was assumed that stem cells remain primitive, mature when vital after which die. Today, it's more likely that there's a cycle.

“It was thought that melanocyte stem cells remain in an undifferentiated state rather than differentiating and dedifferentiating,” said lead researcher Mayumi Ito, PhD, a professor within the Ronald O. Perelman Department of Dermatology and the Division of Cell Biology at NYU Langone Health in New York City.

The process affects different areas of the hair follicle – within the germinal area the stem cells regenerate, within the follicle bulge they get stuck. A unique environment in each location determines how they alter. This “chameleon-like” property surprised the researchers.

Now that researchers have discovered how gray hair occurs, the following step is to seek out a solution to stop it.

“Our study suggests that relocating melanocytes to the right location in the hair follicle may help prevent gray hair,” Ito said.

The research has up to now been carried out on mice, reported online April 19 within the Journal NatureHowever, the findings might be transferable to humans.

“Since the structure of hair follicles is similar in mice and humans, we speculate that human melanocytes may also exhibit plasticity [or ability to change] during hair regeneration,” said Ito.

An indication of melanoma?

The study may have implications for melanoma. Melanomas are cancers that develop from the identical pigment cells called melanocytes. Unlike other tumors, they will renew themselves. This “plasticity,” or ability to alter easily, makes melanoma difficult to eradicate and essentially the most serious type of skin cancer.

“Our study suggests that normal melanocytes are highly plastic and can reverse a differentiation state. Melanoma cells are known to be very plastic,” said Ito. “We believe that this property of melanoma may be related to the high plasticity of primordial melanocytes.”

The discovery that melanocyte stem cells “are more plastic than perhaps previously thought … certainly has implications for melanoma,” said Dr. Melissa Harris, associate professor within the department of biology on the University of Alabama at Birmingham.

Hair-raising detail

Hair follicles are tiny, so the research required sophisticated technologies. Ito and his colleagues used techniques reminiscent of 3D intravital imaging and single-cell RNA sequencing.

This precision allows them to trace stem cells as they age and move inside each hair follicle in near real time.

“This paper uses a winning mix of classical and modern techniques to answer a question that many in the field of pigment biology have long suspected. Not all dormant melanocyte stem cells are the same,” said Harris. (She was lead creator of a Study from January 2021 who proposed a mix treatment to reverse stem cell loss and hair graying.)

Unanswered questions

“The only question not answered in this paper is how to reverse the dysfunction of the melanocyte stem cells that are 'stuck' in the hairline,” Harris said. “There are numerous clinical case studies in humans showing drug-induced hair repigmentation, and perhaps these cases are examples of how dysfunctional melanocyte stem cells 'unstick'.”

“The outstanding concept of this article is that the melanocyte stem cells become 'stranded' and do not receive the proper signal to amplify and migrate appropriately to supply pigment to the hair shaft,” said Dr. Paradi Mirmirani, a dermatologist who makes a speciality of treating individuals with hair disorders and is a school member of the American Academy of Dermatology.

Giving stem cells the proper signals to maintain them motile and mature will be difficult, “but the first step is always to understand the basic underlying mechanism,” said Mirmirani, who practices in Vallejo, Calif. “It would be interesting to see if other factors such as smoking, stress and others affect melanocyte stem cells in the same way.”