Stem Cells in the Skin
by William E. Lowry, Ph.D

The skin is a complicated organ critical to survival because of its ability to keep harmful elements out of the body while retaining fluids in the body. Without this barrier function, the body would dehydrate quickly and would be susceptible to toxins and infections.  

The skin is made up of two principle layers of different kinds of cells. The bottom 90% of skin known as the dermis is defined by a thick layer of cells, blood vessels, and nerves, and provides structural support. The outer 10% of skin is known as the epidermis and is separated from the dermis by a matrix of protein that acts to provide adhesion between the layers but also allows for communication between the two.   Interspersed throughout the skin, hair follicles protrude out of the epidermis.  

Perhaps because of the constant exposure to environmental insults, the epidermis is one of the most rapidly self-regenerating tissues in the body, replacing itself every two weeks in humans. In order to do this a population of stem cells must constantly replenish the supply of rapidly dividing cells. Currently, it is thought that there may be several different kinds of adult skin stem cells found in both the dermis and epidermis including dermal stem cells, melanocyte stem cells, and epidermal stem cells. While non-epidermal stem cells may have enormous potential, the epidermal stem cells were the first and remain the best characterized stem cells in the skin.

Epidermal stem cells are thought to reside in the hair follicle in a structure known as the bulge, though some may be interspersed between hair follicles. The bulge provides a protected niche where stem cells are sheltered from their environment, but also where they are thought to receive signals that tell them to become activated or to remain quiescent (inactive).

Hair follicles undergo dramatic cycles of rest and growth that are thought to be controlled by specific signals that affect the stem cells of the bulge. The challenge for scientists is to find out how these signals work to affect stem cells, how they activate the cells, and how the cells differentiate into the specialized cells of the hair follicle.

Recently it was demonstrated that when individual bulge cells from a normal mouse were removed and grafted onto a hairless mouse, some were able to form stretches of skin with tufts of hair, demonstrating that bulge stem cells can divide to create all of the cell types of the epidermis and hair follicle. This study is relevant not only to growing new hair where previously there was none, but also to improving skin graft techniques. It was shown years ago that skin could be grafted from healthy areas of the body to aid in repair of wounds and burns.

Image of nude mice (mutant strain devoid of hair), which have received a graft on their backs of cells derived from one single bulge cell. This cell was able to generate most skin cell lineages, even hair. Kindly provided by Drs. Cedric Blanpain and William E. Lowry at the Rockefeller University , New York .

Some patients with severe injuries do not have enough healthy skin available for a graft. Stem cells could be isolated from human skin, expanded in culture and grafted back onto patients to regenerate functional skin.   Currently, cultured skin grafts for burn victims do not have hair follicles, sweat glands and other features of normal skin.  Understanding the properties of skin stem cells that can differentiate into all cell types of the epidermis and hair follicle may help to alleviate this problem in the future. 

In addition, scientists have recently shown that mouse embryonic stem cells can be differentiated in culture to form a multilayered epidermis with an underlying dermal layer, similar to normal skin. This skin provides a powerful tool for studying the mechanisms involved in skin development and holds promise for the clinical application of bioengineered skin in the future.

William E. Lowry, Ph.D., is a skin stem cell specialist at the Rockefeller University, New York.

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Updated: February 2, 2005