Category Archives: Dermal Papilla Cells

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.

Bioengineering Approaches to Hair Regeneration: Kageyama

Recently, Yokohama National University (Japan)’s Dr. Tatsuto Kageyama published a very lengthy and detailed paper in a Japanese scientific journal called Journal of the Society of Bioengineering. Dr. Kageyama works at the renowned Fukuda Lab in Japan, which is led by Dr. Junji Fukuda. The actual paper is in Japanese and is titled: “Bioengineering approaches for hair follicle regeneration.

I have translated it and will break out the main details in this post. Besides discussing his team’s scientific approach to hair regrowth, Mr. Kageyama also outlines their overall progress and future plans (though he gives on exact dates for clinical trials). Make sure to check out the diverse range of Google Scholar citations for Mr. Kageyama. In most of his important hair growth related papers, he is a co-author with Dr. Fukuda and others.

Previously, I also mentioned that Ayaka Nanmo, Tatsuto Kageyama and Junji Fukuda are co-founders of a new company named TrichoSeeds. It aims to provide “hair regeneration medicine.”

Bioengineering Approaches for Hair Regeneration

To start off, Mr. Kageyama outlines the three main methods of hair regeneration that his team at Fukuda Lab is working on:

  1. Mesenchymal cell transplantation. Reactivates existing weakened hair follicles by injecting mesenchymal stem cells.
  2. Hair follicle primordium transplantion. See their pending patent on hair follicle primordia.
  3. Hair follicle regeneration. The creation of brand new hair follicles in those who have none left. See their January 2024 study on the large-scale preparation of hair follicle germs (HFGs). The transplantation of HFGs in mice resulted in highly efficient “de novo” hair follicle regeneration.
Bioengineering Approaches to Hair Regeneration
Bioengineering Approaches to Hair Regeneration. Journal of the Society of Bioengineering Volume 102, Issue 4 (2024). Tatsuto Kageyama.

I am most excited about the first method for now since it will come to market first. Especially in aging Japan, where autologous regenerative medicine treatments are going to be speed tracked to in-clinic use. In fact in my recent post titled “A Visit to Fukuda Lab“, Dr. Junji Fukuda had the following quote:

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

If you have a reasonable amount of your own scalp hair remaining, this mesenchymal stem cell injection treatment sounds very promising. The diagram below that Mr. Kageyma published in his new paper is extremely detailed.

Techniques for Culturing Dermal Papilla Cells

Mr. Kageyama discusses his team’s three unique approaches to culturing dermal papilla cells. I covered these methods in various posts and updates related to Dr. Junji Fukuda’s published papers over the past decade.

The conventional dermal papilla culturing method (number 1 below) is similar to Shiseido’s work, which Mr. Kageyama discusses briefly. He says that it has limited effectiveness, since the hair regeneration ability of the cells is reduced during the process of growing mesenchymal cells in a culture dish.

  1. Conventional culturing.
  2. Gel bead culture.
  3. Electrical stimulation culture.
  4. Startified culture.
Mesenchymal Stem Cell Culturing Hair Growth
Mesenchymal stem cell culturing and injection of derma papilla cells for hair growth. Journal of the Society of Bioengineering Volume 102, Issue 4 (2024). Tatsuto Kageyama.

Hair Regeneration by Transplantation of Hair Follicle Primordia

In this second key approach, the aim is to increase the total number of existing hairs. Dr. Kageyama also discusses the work of Dr. Takashi Tsuji and his team in this section of the paper.

The gist of this technology is the mixing of epithelial cells and mesenchymal cells into a single aggregate. This in turn results in the formation of hair follicle primordia (hair seeds), which can then be transplanted into thinning areas of the scalp. The Fukuda team has already succeeeded in the large-scale preparation of hair follicle

At present, the team is conducting experiments in transplanting human hair follicle primordia into mice and improving the regeneration efficiency. At present, there is no guarantee that hair follicle will regenerate from the transplanted seeds. It is also difficult to control the direction of new hair growth with this approach.

Hair Follicle Regeneration

The third and final approach entails the creation of brand new hair follicles for transplantation. i.e., hair multiplication. The Fukuda Lab team has managed to develop a culturing technique for regenerating hair follicles in vitro. The discussion here is fairly technical, so I will just quote (and hope that the translation is accurate):

“Focusing on the self-organization process of epithelial cells and mesenchymal cells, we regenerate mature hair follicles with high efficiency (>99%) by controlling the spatial arrangement pattern of aggregates that form in the early stage of culture. Controlling the spatial arrangement of epithelial cells and mesenchymal cells in the aggregate on the second day of culture from a dumbbell shape to a core-shell shape was the key to in vitro hair regeneration. The production method is very simple, such as adding approximately 2% Matrigel to the culture medium when seeding epithelial cells and mesenchymal cells.”

Hair Follicle Regeneration In Vitro
Hair Follicle Regeneration In Vitro. Journal of the Society of Bioengineering Volume 102, Issue 4 (2024). Tatsuto Kageyama.

Future Plans

The team plans to continue its work in all three approaches to hair regeneration. i.e., transplantation of mesenchymal cells,
transplantation of hair follicle primordia, and transplantation of regenerated hair follicles. Moreover, they have succeeded in constructing microtweezers that can grasp, cryopreserve, and eject hair follicle primordia. They are also working with robotics experts to develop a fully automated transplantation robot.