Wnt Signaling Pathway - Bernstein Medical - Center for Hair Restoration
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Summary of “Hair Regrowth Following a Wnt- and Follistatin-Containing Treatment: Safety and Efficacy in a First-in-man Phase 1 Clinical Trial,” which was originally published in the November 2011 issue of the Journal of Drugs in Dermatology (Volume 10, Issue 11). ((Zimber MP, et al. Hair regrowth following a Wnt- and follistatin containing treatment: safety and efficacy in a first-in-man phase 1 clinical trial. J Drugs Dermatol. 2011 Nov;10(11):1308-12.))

Researchers were aware of the importance of follistatin, a binding protein; Wnt 7a, a signaling protein; and wound healing factors on hair growth. In this study, researchers tested the safety and efficacy of an injection of a mixture of naturally derived molecules on hair growth.

The mixture called the Hair Stimulating Complex (HSC), contained follistatin, as well as keratinocyte growth factor (KGF), and vascular endothelial growth factor (VEGF). The mixture also showed activity similar to the Wnt signaling protein.

The 26 subjects, each suffering from androgenetic alopecia or common baldness, were given an injection of the mixture. The researchers found that there were no adverse events upon injection. Biopsies taken at 22 and 52 weeks showed no abnormal morphology at the injection site.

The sites were also studied at 12 weeks and 52 weeks to determine the effects of the HSC injection in a bald area on the scalp. At 12 weeks after the injection, hair shafts had increased in thickness by 6.3% and terminal hair density increased 20.6%. At 52 weeks, there was a statistically significant increase in total hair count.

Results of the study suggest that injection of the HSC mixture improved hair growth in people with androgenetic alopecia and that previous research with Wnts, follistatin, and growth factors associated with wound healing and regeneration has been substantiated.

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Following some new research on stem cells, and their relationship with androgenetic alopecia (genetic hair loss), an article on stem cells and the way they organize hair growth was published in the April 29th issue of the journal Science.

At issue is not the conversion of hair follicle stem cells into the progenitor cells that stimulate hair growth, as with the prior research, but the ways in which large numbers of stem cells coordinate the cycle of hair growth over thousands of hair follicles. How do all of those hair follicle stem cells know when to grow hair, and how do they know what their “neighbor” hair follicles are doing?

The researchers studied hair growth patterns in rabbits and mice and discovered that certain types of molecules, which were previously known to act as a signaling mechanism for stem cells in maintaining an individual hair follicle’s growth cycle, were also important in enabling large groups of stem cells to coordinate their activity.

The scientists found that hair stem cells coordinate their regeneration with each other with the aid of a pair of molecular activator WNT and inhibitor BMP. When WNT and BMP signals are used repetitively among a population of thousands of hair follicles across the entire skin surface, complex regenerative hair growth behavior emerges via the process of self-organization.

Perhaps more importantly, they found that the stem cell communication pathway present in rabbits and mice is far more robust than in men and women.

“When each human hair follicle wants to regenerate, it can only count on itself; it’s not getting help from other follicles,” Chuong said. “But when a rabbit hair follicle regenerates, it can count on two inputs: its own activation, and the activation signal from its neighbors. Rabbits have a very active hair growth, and that is essential for their survival in the wild.”

The article suggests that if there was a way to manage that process in humans, or “turn back on” the stem cell communication process in human hair follicles, then a treatment could be developed which would substantially increase the number of hair follicles that produce healthy hair.

Read a summary of this new research at ScienceDaily.com.

For more discussion on recent research, visit the Hair Cloning topic.

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Dr. Angela Christiano of Columbia University in New York and a team of scientific researchers have identified a new gene involved in hair growth. Their discovery may affect the direction of future research for hair loss and the diagnosis and ultimate prevention of male pattern baldness.

The condition which leads to thinning hair is called hereditary hypotrichosis simplex. Through the study of families in Pakistan and Italy who suffer from this condition, the team was able to identify a mutation of the APCDD1 gene located in chromosome 18. This chromosome has been linked to other causes of hair loss.

According to Dr. Christiano, “The identification of this gene underlying hereditary hypotrichosis simplex has afforded us an opportunity to gain insight into the process of hair follicle miniaturization, which is most commonly observed in male pattern hair loss or androgenetic alopecia.”

The mutation of the APCDD1 gene inhibits the Wnt signaling pathway. Although this recently discovered gene does not explain the complex process of male pattern baldness, the importance of this discovery lies in the Wnt signaling that the gene directs, has now been shown to control hair growth in humans, as well as in mice.

Reference: Nature 464, 1043-1047 (15 April 2010) | doi:10.1038/nature08875;

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Dr. Bernstein summarizes an article on stem cells that was published in the journal Nature:

This study demonstrates that after wounding the skin of an adult mouse, an embryonic-like change in the epidermal cells outside of the hair follicle stem cells can be induced to form new hair follicle stem cells. In other words, these cells originate from epidermal skin cells in the wound, but then are able take on the characteristics of hair follicle stem cells and actually produce hair. These regenerated hair follicles establish a stem cell population that can produce a hair shaft and continue through all stages of the follicular cycle. The research suggests that these regenerated hair follicles grow new hair through the introduction of Wnt proteins.

The technology, developed at the University of Pennsylvania School of Medicine, has been licensed by Follica Inc. a privately held medical device company.

Reference: “Hair Follicle Regeneration in Adult Mouse Skin After Wounding,” Ito, M., et al. Nature 447, 316-320, May 17, 2007

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