What is Hair Follicle Neogenesis? - Hair Follicle Neogenesis
Hair Loss Guide

What is Hair Follicle Neogenesis?

In this article, I explain the cutting-edge methodology that’s gaining traction in the field of hair loss: wound-induced hair follicle neogenesis, or WIHN. I will tackle some basic concepts about this technique, as well as the scientific research that supports its effectiveness.

What is wound-induced hair follicle neogenesis (WIHN)

For a long time, scientists believed that the number of hair follicles in the human body is fixed after embryogenesis. In other words, all the hair follicles a person has are predetermined during the early stages of embryonic development with no new follicle formation after birth.

However, researchers found that the process of hair follicle neogenesis is possible during wound healing.

This relatively new finding astonished scientists and opened the door for a multitude of potential therapeutic approaches.

In simple terms, WIHN is the formation of new hair follicles in areas that didn’t previously have any hair or areas that were damaged by the large spectrum of alopecia disorders.

History of WIHN

Wound-induced hair follicle neogenesis was originally described in rats and rabbits during the 1940-1950s. Back then, scientists noticed that these lab animals grew new hair follicles after undergoing a traumatic injury in hair-free areas.

These findings intrigued the scientific community, so some researchers started investigating the biological processes involved in this phenomenon.

Because embryonic-induced neogenesis was a futuristic aspect back then, scientists largely forgot about WIHN.

After a few decades, the topic of WIHN returned to the spotlight with several scientific papers published every year that attempt to explain the biology of the process.

Nowadays, WIHN is being intensely researched in the hope of inspiring scientists to come up with a novel treatment for hair-related disorders.

The physiology of WIHN

To understand wound-induced hair follicle neogenesis, we first need to understand how hair follicles form during embryogenesis.

The major driver of this process is the Wnt signaling pathway, which entails a complex intracellular signaling cascade that’s responsible for the degradation of β-catenin.

This protein is constantly metabolized when the Wnt signaling pathway is turned on; however, once the Wnt peptide binds to a special intramembrane receptor, β-catenin starts to accumulate inside the cell and then translocate into the nucleus to stimulate DNA expression of proteins, thus determining the fate of that cell.

Leading researchers believe that a similar process occurs during WIHN.

However, most of these findings were noted in mice, which begs the question: what’s so special about mice?

When researchers started looking into this, they found that mice possess special cells known as gamma-delta dermal cells, which significantly grow in number post-injury. Moreover, the production of the growth factor FGF-9 is robustly activated during this phase.

These two factors are believed to play a major role in the physiology of WIHN, which explains why humans tend not to naturally develop new hair follicles during wounding.

As for the role of FGF-9, scientists theorize that it stimulates the dermal fibroblasts to secrete Wnt, starting the intracellular cascade that I( explained above.

Research around WIHN

As I mentioned earlier, dozens of papers are published every year to explain the process of WIHN and how we could implement this fascinating physiology to treat hair disorders in humans. Let’s examine some of the notable studies.

Study 1

In a 2018 study, scientists surveilled an 80-year old patient who had undergone surgical excision of basal cell carcinoma.

After a while, the scar healed very well, but his physicians noted that there was hair growing at the center of the wound. This grabbed the attention of the researchers since it was the first case study that reported WIHN in humans.

Researchers stated that “this case demonstrated that neogenesis of hair is possible even in geriatric patient. To the best of our knowledge, this is the first report of hair regrow in human skin after wound healing.”

Unfortunately, the patient refused to go through more biopsies, which limited our understanding of the mechanisms involved.

Study 2

A 2018 study analyzed the molecular and biological phenomena that occur during WIHN. Scientists found that fibroblast growth factor 9 (FGF-9) plays a major role in this process, stimulating the growth of dermal papilla.

Moreover, FGF-9 antagonists were shown to significantly decrease the number of new hair follicles.

The same study found that other pro-inflammatory compounds, such as tumor necrosis factor (TNF), interleukin-6 (IL-6), prostaglandin E2, and the hedgehog signaling pathway were all capable of activating the process of WIHN.

In contrast, prostaglandin D2 was shown to inhibit WIHN.

The study ended by stating that “WIHN research not only allows further exploration of better clinical therapies for hair-related disorders but also contributes to the overall investigation of biological growth and regeneration.”

The aforementioned compounds are all part of the inflammatory response that occurs during the wound-healing phase.

Molecules, such as TNF, IL-6, and prostaglandins, are secreted by immune cells, including macrophages, neutrophils, and basophils.

This could be a gateway to develop future therapeutic approaches to alopecia and hair disorders in general.

Study 3

Collagen VI plays several roles in the physiology of the skin, but there is no clear correlation between this molecule and hair follicle growth.

However, in a 2015 study, scientists found that the lack of collagen VI post-injury drastically increases WIHN.

Researchers believed that collagen VI has an impact on the Wnt signaling pathway and that its abundance can halt WIHN; they concluded; “we found that the enhanced wound-induced hair regrowth in mice is abolished by treatment with purified collagen VI. Altogether, this study provides evidence on the role of specific ECM molecules in wound-induced hair regrowth, and sheds light on the potential therapeutic benefit in accelerating impaired hair growth by targeting collagen VI.”