Category Archives: Stem Cells

Foxc1, Nfatc1, Rui Yi, Stem Cells

Escaping Hair Follicle Stem Cells

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Dr. Rui Yi and his team from Northwestern University’s YiLab just published a groundbreaking new paper explaining the reason for aging related hair loss. The current findings were shown in various mammals.

Escaped hair stem cells.
Escaped stem cells in aging hair follicles. Source: Nature Aging (2021). Zhang, C., Wang, D., Wang, J. et al.

The Great Stem Cell Escape

The findings in this paper suggest that hair loss is not caused by stem cell death, depletion and exhaustion as has long been postulated. Rather, the stem cells escape from the structures that house them (i.e., the hair follicle bulge). The New York Times has an in-depth summary of these very interesting findings. Also see another take from Futurism.

In order to flee, the cells change their shapes from round to amoeba-like structures. Then they squeeze out of tiny holes in the follicle. Finally, they recover their normal shapes and dart away!

Of note, the researchers (led by Dr. Yi and his PhD student Chi Zhang) discovered two genes (Foxc1 and Nfatc1) that were less active in older aging hair follicle cells. The role of these two genes is to to “imprison” stem cells in the bulge. Note that Foxc1 stands for Forkhead Box C1. Nfatc1 stands for Nuclear Factor of Activated T Cells 1.

This study found a “hitherto unknown activity” of epithelial cells escaping from their niche during the aging process. This escape subsequently leads to stem cell degradation.

“If I did not see it for myself I would not have believed it. It’s almost crazy in my mind.” — Dr. Yi.

Foxc1 and Hair Loss

Note that I have covered Foxc1 in two past posts. The first (“COL17A1 damage and hair turning into skin“) covered a 2016 study whose co-author was also Dr. Rui Yi. Key quote:

“In self-renewing stem cells (SCs), Foxc1 activates Nfatc1 and bone morphogenetic protein (BMP) signaling.”

The second post covered a 2016 article from Dr. Elaine Fuchs. In it, she found that Foxc1 plays a critical role in hair follicle and hair color (melanocyte cell) stem cell regenerative capabilities.

Stem cells residing in hair follicles are held in an inactive state for long periods of time. The new findings showed that these quiescent periods are essential for maintaining the stem cells’ rejuvenating potential.

On a somewhat related note, Dr. Yi and his team also published a new paper in September 2021 in relation to miRNA and hair loss. I have added it in that related post.

Pietro Gentile, PRP, Scalp Tissue Micrografts, Stem Cells

Dr. Pietro Gentile, Hair Follicle Stem Cells and PRP

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Over the past few years, I have heard a lot about Dr. Pietro Gentile of Italy and his unique work in the hair loss field. His website and his Instagram have some interesting content. However, both are lacking relative to the higher quality of his numerous research papers.

Dr. Pietro Gentile and PRP

I originally learnt about Dr. Gentile via his collaboration with Dr. John Cole and Chiara Insalaco. In 2017, the three of them authored a paper comparing non-activated PRP versus activated PRP.

In my detailed post on the effectiveness of PRP for hair loss, I listed around 40 studies at the bottom. Of that total, 5 were authored by Dr. Gentile. On his website, the doctor has several pages devoted to PRP for hair loss and PRP for facial cosmetic treatments.

Hair Follicle Stem Cells

Micrograft Stem Cell Transplant Hair Growth Before After -- Pietro Gentile
Micrograft Stem Cell Hair Transplant Before and After in a 38-year old Female. Copyright © 2020 Pietro Gentile et al.

More interestingly, Dr. Pietro Gentile has in recent years published a number of papers on stem cells and hair growth. Most recently, in January 2020, he authored a paper titled “Autologous Micrografts from Scalp Tissue“. The conclusion was that micrografts containing autologous human hair follicle mesenchymal stem cells (HF-MSCs) could represent a safe and viable hair loss treatment.

The autologous micrografts of HFSCs were prepared using the doctor’s proprietary “Gentile Protocol”. Instead of harvesting hair follicle grafts like in a hair transplant, this process entails harvesting scalp tissue and associated hair follicle stem cells. I think that this tissue extraction can also be from outside the typical permanent hair donor zone. Dr. Gentile published the outline of his hair follicle stem cell isolation technique in an earlier paper from 2017.

Autologous Micrografts of Hair Follicle Stem Cells
Autologous Micrograft Injections of Hair Follicle Stem Cells (HFSCs) in a 41-year old Male with Androgenetic Alopecia. Before and After (58 Weeks). Copyright © 2020 Pietro Gentile et al.

Other Findings

in 2019, Dr. Gentile published a study on Adipose Tissue-Derived Hair Follicle Stem Cells (HD-AFSCs) improving hair growth and density. Make sure to read my past posts on adipose stem cells and hair growth. The doctor has also published a number of papers in the past on stromal vascular fraction, especially in regenerative plastic surgery and scar reduction applications.

In 2020, Dr. Gentile and his team found that a combination PRP + Microneedling + Laser treatment protocol led to great hair growth results. However, hard to tell which of the three made the most impact.