Newly Identified Skin Stem Cells Strikingly Similar to Those Found in Embryos

Recent findings show that a new type of stem cell found in the skin acts similarly to certain stem cells found in embryos.  Like embryos, these stem cells can generate fat, bone, cartilage, and even nerve cells. According to HHMI International Research Scholar, Freda Miller, these newly-identified dermal cells may prove useful for treating persistent wounds or even neurological disorder. These cells were first noticed several years ago in rodents and humans but have only now been confirmed as stem cells. These cells are capable of self-renewal and can even grow into cell types that make up the skin’s dermal layer under the right conditions. This is particularly interesting in our industry because the dermal stem cells also appear to help form the basis for hair growth.  This new work was published in its entirety December 4, 2009, in the journal Cell Stem Cells.

Miller’s team examined the dermal layer of the skin in both mice and people. The dermis is a thick layer of cells in which hair follicles and sweat glands are rooted. In 2001, Miller’s team had a remarkable revelation when they discovered cells that respond to the same growth factors that make brain stem cells differentiate. She named them skin-derived precursors (SKPs, or ‘skips’).  Miller later discovered that these cells acted like neural crest cells from embryo (stem cells that generate part of the nervous system and head.  Despite SKPs resemblance to stem cells in Petri dishes, Miller was initially unsure if they would behave the same way in the body.  A team member, therefore, performed a series of experiments to test whether SKPs did behave similar to stem cells in the body.

Previous work had shown that the SKPs produce a transcription factor called SOX2, one produced in many types of stem cells. The team used genetically engineered mice with SOX2 genes tagged with green fluorescent protein, which allowed them to track where SOX2 was expressed in the animals. They found that about 1% of skin cells from adult mice contained the SOX2-making cells, and they were concentrated in the bulb at the base of hair follicles. Interestingly, when the team cultured these cells, they began behaving like SKPs.

Miller’s team then decided to see if the cells would, rather than just settling at the base of hair follicles, actually grow new hair. Fluorescent cells were mixed with epidermal cells (both of which make up the majority of cells in a hair follicle) and the mixture was transplanted under the skin of hairless mice. The team was intrigued to find that these mice began growing hair. The team also transplanted rat SKP cells under the skin of mice. Finally, the team gave mice small puncture wounds and then transplanted their fluorescent SKPs next to the wound. Within a month, many transplanted cells appeared in the scar, showing they had contributed to wound healing. The SKPs were also found in new hair follicles in the healed skin.

The cells behaviour (both in wound healing and hair growth) led Miller’s team to conclude that the SKPs are, in fact, dermal stem cells. Miller said the finding complements work by HHMI investigator Elaine Fuchs, who found epidermal stem cells, which help renew the top layer of skin. Miller believes that combining the evidence from the two labs suggests a possible path to hair loss treatments. However, much about the signalling mechanism remains unknown.

Moving forward, Miller wants to investigate less cosmetic applications for these findings, such as treating nerve and brain diseases. She is searching for signals that could trigger the dermal stem cells to rev up their innate wound-healing ability. If such a signal can be found and copied, Miller can envision one day treating chronic wounds with a topical cream. Another possible application: improving skin grafts, which today consist of only epidermal, not dermal, cells. While skin grafts can dramatically help burn victims, those grafts don’t function like normal skin.