Science subjournal: Successfully cultivate fully mature hair follicles in culture

A team of researchers from Japan studied the process of hair follicle growth and hair pigmentation, and successfully cultivated hair follicles
in culture.
Their in-vitro hair follicle model increases understanding of hair follicle development and helps develop useful applications
in the treatment of hair loss diseases, animal testing, and drug screening.

During embryonic development, there is an interaction
between the outer layer of the skin, known as the epidermis layer, and the connective tissue, called the mesenchymal.
These interactions act like messenger systems that trigger follicular morphogenesis
.
Morphogenesis is the process by
which cells in an organism are organized into tissues and organs.

Over the past few decades, scientists have used animal models to explore key mechanisms
related to the development of hair follicles.
Since it remains challenging to fully understand the mechanisms of these follicle development, follicular morphogenesis has not been successfully replicated
in laboratory dishes.

Recently, organoid culture has received a lot of attention
.
Organoids are tiny, simple versions of organs — scientists produce them and use them in laboratory dishes to study the development and pathology
of tissues and organs.
"Organoids are a promising tool to elucidate the mechanisms of hair follicle morphogenesis," said
Tatsuto Kageyama, assistant professor at Yokohama National University's School of Engineering.

Using a fairly low concentration of extracellular matrix, the research team synthesized hair follicle organs
by controlling the structure produced by two embryonic cells.
The extracellular matrix is the body's framework, providing structure
for cells and tissues.
The extracellular matrix adjusts the spacing between the two types of embryonic cells from dumbbell to core-shell
.
Newly formed hair follicles with typical features appear in the nucleoshell-like group
.
These nucleoshell-like groups increase the contact area between the two cell regions to enhance the mechanism
that promotes hair follicle growth.

The organoid culture system developed by the team generated hair follicles and hair shafts
with almost 100% efficiency.
Follicular organoids produce fully mature hair follicles with long hair stalks (about 3 mm long after 23 days of culture).

When this growth occurs, researchers can monitor hair follicle morphogenesis and hair pigmentation in vitro to understand the signaling pathways
involved in this process.

The researchers examined the feasibility
of hair follicle organs for drug screening and regenerative medicine.
They then added to the medium a drug that stimulates melanocytes, which plays a key role
in producing hair color coloring.
After adding this drug, the researchers significantly improved the pigmentation
of hair-like fibers.
In addition, by transplanting hair follicle organoids, they achieved efficient follicle regeneration with repeated hair cycles
.
They believe that in vitro hair follicle models are important for understanding hair follicle induction, evaluating hair pigment and hair growth drugs, and follicle regeneration
.

The researchers' findings may also prove relevant to other organ systems, helping to understand how physiological and pathological processes develop
.
Looking ahead to future research, the team plans to optimize their organoid culture system
with human cells.
"Our next step is to use cells from humans and apply them to drug development and regenerative medicine," said
Professor Junji Fukuda of the School of Engineering at Yokohama National University.

Their future research may eventually open new avenues
of research for the development of new therapeutic strategies for hair loss disorders such as androgenetic alopecia that is common in both men and women.

The research team included Katsuto Kageyama from Yokohama National University, Kanagawa Institute of Industrial Science and Technology, and Japan Science and Technology Agency; Akihiro Shimizu, Riki Anakama, Rikuma Nakajima and Kohei Suzuki of Yokohama National University; Yusuke Okubo of the National Institute of Health Sciences; and Junji Fukuda
from Yokohama National University and Kanagawa Institute of Industrial Science and Technology.

Funding provided by the Japan Agency for Science and Technology; Ministry of Education, Culture, Sports, Science and Technology, Kanagawa Institute of Industrial Science and Technology, Japan Medical Research and Development Agency, Sumitomo Foundation, Hoya Science Foundation, and Kao Melanin Seminar
.