Growth factor protein promotes thicker hair

Growth factor protein promotes thicker hair

Scientists in Boston, USA, claimed they have found a protein normally associated with blood vessel growth that also makes hair follicles bigger. Dr. Michael Detmar, associate professor of dermatology at Massachusetts General Hospital in Boston, who led the study compared two groups of mice one "wild-type" and the other genetically bred to produce extra vascular endothelial growth factor (VEGF) in the skin.

The scientists found, the mice with extra VEGF grew fur faster and thicker in the first two weeks of life. When the mice were shaved at two months of age, they grew back fur that was 70 percent thicker than "wild-type" mice. Blood vessels surrounding their fur follicles were also larger and when they treated normal mice with a drug that blocks VEGF, their fur grew in thin and developed bald spots. "So by modulating VEGF production in the skin, we can directly influence the size of the hair," Detmar said.

"In male pattern hair loss, it's not that the follicles are gone. They're just miniaturized" said Detmar. "If anyone could find a way to make the follicles bigger, men might grow hair again." The key, he and colleagues report in the Feb. 19 issue of the Journal of Clinical Investigation, might be a protein called VEGF now used experimentally to help people grow their own heart bypasses.

VEGF, or vascular endothelial growth factor, helps the body grow blood vessels. It can help heart disease patients and is one of the proteins blocked in certain experimental anti-cancer therapies aimed at starving out tumors. The researchers are now working on a way to get VEGF into the scalp in a cream or ointment. "The question now is can we, by this method, improve hair growth in humans?" said Detmar. "Applying it to humans will be a big challenge."

Vascular Endothelial Growth Factor (VEGF) is a naturally produced chemical called a cytokine. Cytokines are a signalling mechanisms that cells use to communicate with each other. cells with approriate cytokine receptors react in specific ways when they receive a signal. As its name suggests, VEGF stimulates endothelial cells of blood vessels to proliferate and grow, a mechanism celled angiogenesis (angio=blood vessel, genesis=formation).

VEGF was originally identified in tumor biology. Tumors grow very large very rapidly and to do this they need a lot of nutrients. To ensure a good supply, tumor cells may produce VEGF to induce blood vessels in surrounding healthy tissue to grow into the tumor. VEGF production and increased angiogenesis can also bee seen in wound healing and in some diseases such as psoriasis. However, VEGF is also produced by normal, healthy cells in various organs to maintain a good blood supply.

VEGF as a stimulator of hair growth is not a new idea. Several studies looking at product expression have demonstrated VEGF production in various hair follicle compartments. Hair folicles have a cycle of growth, called anagen and rest, telogen. When hair follicles are resting they are relatively small an inactive, but when they enter a growth phase they become much larger and the cells of growing hair follicles are the fastest proliferating non-tumor cells in the body. To enable this increased cellular activity, a good nutrient supply is required and it has been shown that as hair follicles leave telogen and enter anagen, angiogenesis is stimulated. An intricate network of blood vessels forms and surrounds hair follicles as they enter anagen.

This study is a significant step in our understanding of hair cycle control and is the first to perform functional assays on hair follicle growth under the influence of VEGF. The scientists were previously involved with examining VEGF and angiogenesis in skin tumors and other inflammatory skin diseases. For their studies, they produced a genetically mutated (transgenic) mouse that consistently over expresses VEGF in the skin. In their previous studies they noted that the skin developed a very extensive system of blood vessels and they hypothesised that this might affect hair follicle activity.

This study examined tissues from the transgenic high VEGF expressing mice for the extent of angiogenesis around hair follicles, measured the size of the hair follicles, and compared these statistics with those from normal mice. In addition, the researchers injected an antibody that blocks VEGF activity into normal mice and also exposed cultured hair follicle cells to VEGF. They found that the transgenic mice had significantly larger anagen hair follicles in association with VEGF production and angiogenesis as compared to normal mice. Blocking VEGF activity resulted in a delay of hair follicles switching from telogen to anagen and much smaller anagen hair follicles developed. Their culture studies showed that VEGF had no direct stimulatory effect on hair follicle growth. That is, it was the formation of blood vessels that allowed increased hair follicle activity in the mutated mice and not any direct effect on the hair follicle cells by the VEGF signal. The study concludes that VEGF has an important role in controling hair biology and that hair follicle size is partly dependant on VEGF induced angiogenesis.

Previously it has been suggested that impaired angiogenesis may play a role in androgenetic alopecia. However, while VEGF seems to have a significant indirect effect on hair follicles, it does not act in isolation. Many cytokines and other factors can stimulate or inhibit hair follicle activity. Whether hair follicle growth could be stimulated by injecting VEGF or the DNA coding for VEGF into skin remains to be seen. There are potential side effect risks as the angiogenesis would not be restricted to the hair follicles. There will also be other limiting factors involved including the natural production in normal skin of angiogenesis inhibiting factors. The maximum possible size of a hair follicle is probably limited by the size of the dermal papilla and an upper limit to the level of activity by these cells. Most likely then, gene therapy for hair loss could involve VEGF, but in itself this may not be enough. A cocktail of DNA coding for several genes is probably required.