Category Archives: Dermal Papilla Cells

Oxytocin, Cinnamic Acid and Hair Growth

Update: October 14, 2024

Oxytocin Receptor Agonists

A third study in relation to oxytocin and hair growth has been published by the same Japanese team of Fukuda, Kageyama, Seo and Lan (h/t “Ben”). This one is titled: “Effects of oxytocin receptor agonists on hair growth promotion.”

The researchers findings from October 2023 (see next section) showed the hair growth promoting effects of oxytocin (in hair follicle organoids). However, the clinical use of oxytocin is difficult due to its rapid degradation in vivo and poor permeability due to a large molecular weight.

Looking for alternatives, in February 2024 (see bottom of this post), the Japanese team reported that cinnamic acid promoted hair growth via the activation of oxytocin receptor (OXTR) expression.

And now in October 2024, the researchers have found that oxytocin receptor agonists WAY267464 and LIT001 increased the expression of hair growth-related genes in dermal papilla cells. And they significantly promoted hair “follicle sprouting”. According to “Ben”, both WAY267464 and LIT001 are endogenous, already synthesized and purchasable.

April 16, 2024

Oxytocin and Hair Growth

In October 2023, Japanese researchers (led by Junji Fukuda and Tatsuto Kageyama) published an interesting paper that concluded that oxytocin has a positive effect on hair growth via upregulation of dermal papilla cell signature markers. These findings were later covered by a NHK News video report from Japan.

Oxytocin (OXT) is better known as the “love hormone”. It is produced and released by women during childbirth and lactation. It is also produced during skin stimulation, such as when hugging or getting a massage. OXT is also called the anti-stress hormone.

In this study, OXT treatment resulted in the upregulation of genes that were associated with hair growth promoting factors. These included VEGFA (a protein encoded by the VEGF gene), PDGFB, FGF7 and BMP2. This ultimately results in peg-like hair sprouting via the improved hair growth ability of dermal papilla cells.

Oxytocin Hair Growth
Oxytocin and Hair Growth. Source: Nature, 20 October, 2023. Fukuda et al.

Cinnamic Acid, Oxytocin Receptor Activation and Hair Growth

I was 50/50 about writing a post on oxytocin and hair growth. We have seen numerous such past unusual examples that ultimately lead to no actual hair loss products.

However, in February 2024, the same researchers from Japan published yet another study that found cinnamic acid to promote hair growth via the activation of oxytocin receptor (OXTR) expression. Cinnamon is officially known as Cinnamomum cassia, and cinnamic acid is a component of Cinnamomum cassia.

“Treatment with cinnamic acid led to upregulation of OXTR and trichogenic gene expression in human dermal papilla (DP) cells.”

Three people e-mailed me the story about these findings that was published on phy.org several weeks ago. And a few others also posted blog comments about this news. No-one seemed to connect both these Japanese studies if I recall correctly.

Cinnamic Acid Oxytocin Hair Growth
Cinnamic Acid, Oxytocin Receptor Activation and Hair Growth. Source: Nature, 27 February, 2024. Fukuda et al.

Note that cinnamic acid can also be derived naturally from a number of plants. The most famous being cinnamon, shown in the image above. Yet one more ingredient to add in the list of natural treatments for hair loss.

A 2012 study from Japan found that cinnamon extract promotes Type I collagen biosynthesis via the activation of IGF-I signaling in human dermal fibroblasts. Also from 2012, a study from Taiwan concluded that cinnamic aldehyde (a constituent of Cinnamomum cassia) has excellent anti-inflammatory properties.

A 2018 study from Taiwan found that Cinnamomum osmophloeum Kanehira (COK) leaves caused dermal papilla cell proliferation and increased hair growth in mice.

A Visit to Fukuda Lab at Yokohama National

Update: July 5, 2024

Fukuda Method versus Tsuji Method

A unique and interesting new interview with Dr. Junji Fukuda (h/t “Theo”). He discusses in detail the difference between his team’s hair multiplication method versus Dr. Takashi Tsuji’s team’s approach. Dr. Fukuda’s work is being undertaken via a company called TrichoSeeds. Dr. Tsuji’s work is being undertaken via OrganTech.

Dr. Fukuda mentions how the pioneer of hair transplantation (he probably means Dr. Shoji Okuda) is Japanese and one of the pioneers of hair regenerative medicine (Dr. Tsuji) is also Japanese. Shiseido (Japan) could end up also being a pioneer in the hair loss world.

Key quote:

“Dr. Tsuji and his team first extracted hair follicles and increased the epithelial and mesenchymal cells. We did the same thing up to this point. After that, Professor Tsuji and his team created individual hair follicle primordia by massing each type of cell in a centrifuge and combining them under a microscope. We took the approach of mixing epithelial cells and mesenchymal cells extracted from hair follicles in a culture solution and culturing them together.”

He also mentions that when fibroblast growth factor 2 (FGF2) was added to the base medium of Fukuda culture, the efficiency of hair regeneration was significantly increased.

Finally, he mentions the potential cancer side effect that prevents his team from easily creating hair follicles from iPS cells. Japanese laws governing regenerative medicine would allow the use of iPS cells in regenerating vital organs, but not for regenerating hair.

Update: April 18, 2024

New Junji Fukuda interview given to Tokyo Television. Someone please translate if you know Japanese.

Junji Fukuda TV Interview
Junji Fukuda TV Interview.

February 21, 2024

I have covered the work of esteemed and prolific Japanese hair loss researcher Dr. Junji Fukuda for almost ten years. I also wrote the below two detailed posts about his findings. The second of these is very lengthy because I have kept updating it for a few years.

Make sure to check out the Yokohama National University based Fukuda Lab’s hair research page.

A Visit to Fukuda Lab at Yokohama National

Reader “Theo” just sent me a link to a very interesting diary of a hair transplant surgeon from Japan who just visited the Fukuda Lab.

Note that while Dr. Fukuda is based at Yokohama National University, the research seems to be taking place at Kanagawa Life Innovation Center (per the above link). One of the images also mentions the Kanagawa Center for Clinical Research & Strategy (KCCR). Yokohama is the second largest city in Japan and is the capital of Kanagawa Prefecture. Check out this PDF of the regenerative medicine sector at Kanagawa Prefecture.

From this visit and summary, I learn some very interesting things. There are three distinct methods in which Dr. Fukuda is pursuing hair regeneration. I mentioned them in my past lengthy post too, but now we have more clarity.

1) Dermal Papilla Cell Transplantation

“Dermal papilla cell transplantation is about to begin in Japan.

Transplantation of dermal papilla cells (via stratified culture). I assume that the “stratified cuture” in the translation means 3D culturing. Dr. Fukuda mentions that Shiseido already conducted a clinical trial using 2D culturing. In this method, cells are are lined up on a flat surface when culturing, but it only resulted in a 5% increase in hair volume. The 3D method will likely be superior and the clinical trials are about to finally begin! It is hoped to be “put into practical use within five years”.

2) Transplantation of Hair Follicle Primordium

“I think this will take some time.”

The creation of hair follicle primordia means generating hair from scratch. i.e., hair multiplication. I previously discussed the Yokohama team’s process of achieving this via increasing and mixing epithelial cells and mesenchymal cells. These then form “hair follicle primordia“ that are transplanted to the same donor’s scalp in order to regenerate hair in thinning regions of the scalp.

Per the latest feedback from Dr. Fukuda, while this process has already been proven by them in mice, human hair is a different animal. Once the primordium tissue is transplanted to human heads, the direction and length grow haphazardly. He thinks that this will take some time.

3) Transplantation of Regenerated Hair Follicles in Vitro (Organoids)

“It will likely take more than 10 years before it can be used in humans.”

The final method is in vitro regenerated hair follicle transplantation (also called organoid). In this process, hair follicles are regenerated outside the body, lengthened by almost 100%, and then transplanted into the scalp. Per Dr. Fukuda, it will likely take more than 10 years before it can be used in humans.

Other Notes

In March 2023, Dr. Fukuda and his Yokohama team published an important hair regeneration related study. They made an improvement in the expansion of hair follicle stem cells (HFSCs) and dermal papilla cells via the use of a newly designed microwell array device.

The Fukuda Lab has even undertaken research on electric stimulation of human dermal papilla cells for hair regeneration.

So in one day we get two very unique insights and forecasts from Japan! Thanks again to “Theo” for all the stellar non-English language updates from Japan and South Korea.

Fukuda Lab Hair Research
Fukuda Lab’s hair research summary poster. Source:
Naohiro Uchida, Director of Almo Plastic Clinic Hair Transplantation.