Professor George Cotsarelis, University of Pennsylvania
This week, there was some good news for the follicularly challenged, because researchers at the University of Pennsylvania have taken the first steps towards discovering a cure for baldness. They noticed that when wounded skin was healing, some of the cells in the upper layer of the skin, the epidermis, turned into hair follicles. By looking at the genes that were turned on in those cells they were able to isolate a particular genetic pathway that lets hair follicles form during healing in the same way that they did during embryonic development. Chris Smith spoke to Professor George Cotsarelis:
George - The dogma has been that hair follicles do not develop during adulthood, so once you lose a hair follicle, the prevailing wisdom has been that you cannot regenerate it. So, we were surprised to find that actually when we wounded mice, during the healing process we noticed new hair follicles forming in the centre of the wound. On close examination we realised that these follicles were undergoing very similar changes that are found when the hair follicle first develops in the embryo.
Chris - Now, when you say you wounded the skin, do you mean you actually removed a full-thickness piece of skin or just the surface, what did you take away?
George - We actually removed the entire skin, a full thickness on the back of the mouse and allowed it to heal.
Chris - So, if you made a full-thickness injury to the skin that means that the regeneration of those hair follicles, the cells that are doing that must be coming from somewhere else, it is not some deep-rooted stem cell coming in from below the lesion? So, where are those cells coming from?
George - We were first expecting to find new hair follicles to be coming from the stem cells that are actually present in the hair follicles at the periphery of the wound. We were quite surprised to find that, although the stem cells at the periphery of the wound contributed to wound healing, these cells did not contribute to the new hair follicles. What we actually found was that the hair follicles developed from cells in the epidermis and from the upper part of the follicle.
Chris - So, what sort of cells are they then, if they are not follicle cells, what is actually producing the follicles?
George - The epidermal cells that are creating these follicles are essentially reprogrammed and instructed to make a new hair follicle. So, the signals that go between the epidermis and the dermis during the neonatal time period or during embryogenesis are re-utilised in the adult to regenerate new hair follicles on the face of wounding.
Chris - Do you know what the factors are which are provoking those stem cells which are in the skin, because presumably that might be quite an interesting pattern of genes to know about if we want to try and recreate hair follicles in aged men?
George - We know from developmental biologists who have been working on hair-follicle development that the gene beta-catenin, which is in the Wnt pathway, is very important for normal hair-follicle development. So, we looked at beta- catenin and it was being expressed in these new follicles, and we also then blocked beta-catenin after the wound had closed. If you block beta-catenin at that point, then no new hair follicles will form but —perhaps more exciting than that — when we activated the Wnt pathway, we found an increase in the number of new hair follicles that formed, in fact the number doubled. So this indicates that during this wound-healing process, these cells are susceptible to manipulation by signals that are known to be important for hair-follicle development. So, we think that in the future we will be able to design treatments based around the response that we see after wounding.