Finding advances understanding of skin wounds and skin cancer
In a study that has implications for understanding the way skin wounds heal and some skin cancers develop, researchers at the University of Pennsylvania Medical Center and New York University School of Medicine have found compelling evidence that the hair follicle and the epidermis may originate from the same cache of cells.
The researchers have traced the earliest daughters of the stem cells (primitive cells not yet committed to a specific developmental pattern) to the section of the upper follicle adjacent to the region where the stem cells reside.
The finding shows clearly for the first time how cells from the hair follicle can directly influence the epidermis.
"Our results suggest that in normal newborns, and in healing wounds throughout life, it is the daughter cells in the upper follicle that migrate upward to form and maintain the new epidermis. The daughter cells of the stem cells also migrate downward to form the hairshaft," said Robert M. Lavker, PhD., professor of dermatology at the University of Pennsylvania School of Medicine.
Lavker has been investigating stem cell systems for nearly 20 years in collaboration with Tung-Tien Sun, PhD, of the NYU School of Medicine. Their current work identifies the upper follicle as the site of young transient amplyfying (TA) cells -- which are the early offspring of stem cells -- and follows the TA cells’migration into the epidermis and into the bulb, or root, of the hair where the TA cells differentiate into components of the hair shaft.
The current study, which will be published in the August 18 issue of Cell, builds on the 1990 research of Lavker and his coworkers, in which they located stem cells at the bulge of the follicle (the point where the outer root sheath attaches to the arrector pili muscle).
The new study furnishes evidence that these researchers were correct at the time when they also postulated that the bulge stem cells are bipotent – capable of generating TA cells that develop along two distinct paths.
Lavker and Sun had proposed that the stem cells were bipotent in order to explain a phenomenon that scientists had been aware of for years, but had never been able to understand: Healthy skin seems capable of self-regeneration. But when a severe burn destroys the skin, epidermal cells are found to emerge from any remaining hair follicles to re-establish the outer skin in circles of re-growth. The precise origin of those new epidermal cells had never been established.
Lavker and Sun’s theory that bulge stem cells were the source of both epidermal cells and hair cells became the basis of their current research. Using young and adult mice, Lavker, Sun and their colleagues devised a double-labeling technique in which they could follow the division of the stem cells, and then observe the trafficking patterns of the early-offspring TA cells.
Results from the study "strongly suggest that the bulge stem cell is bipotent, and that the daughter (TA) cells migrate up to the epidermis and down to the root," Lavker said.
Added Sun: "There’s been a termendous controversy as to where the epidermal stem cells are. We are proposing that there is just one entity -- an ultimate epidermal stem cell -- located in the bulge area of the hair follicle, that is capable of forming skin or hair."
A major "take home message" of the research, Lavker said, is the pivotal importance of the upper follicle in the healing process of the skin: "It places the upper follicle directly in the center, for wound repair."
The work also paves the way for designing effective skin cancer treatment, by explaining why skin tumors that are produced for the purpose of research frequently originate in the upper follicle.
"In addition to wanting to target stem cells in the bulge for skin cancer (stem cells are the prime source of abnormal growth and mutation), now you also have to consider targeting the upper follicle where the TA cells retain most characteristics of the stem cells," Lavker said.
Participating with Lavker and Sun in the research were Michael Lehrer, MD., and Pamela Jensen, PhD., of Penn, and Gina Taylor, MD., of Presbyterian Hospital. The work was funded by the National Institutes of Health.
Editor’s note: Dr. Lavker may also be reached directly at: 215-898-3232. He will be available for interviews Thursday and Friday, August 10 and 11. Next week he will available all day on Monday and Friday, Aug. 14 and 18, and on the afternoon of Tuesday, Aug. 15.
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