A team of Japanese researchers studying the growth and pigmentation processes of hair follicles has succeeded in generating hair follicles in cultures. Their in vitro hair follicle model adds to the understanding of hair follicle development, which could aid in the development of useful applications in the treatment of hair loss disorders, animal testing, and drug screening.
Their findings were published in Scientists progress October 21.
As an embryo develops, interactions occur between the outer layer of skin called the epidermal layer and the connective tissue called the mesenchyme. These interactions work much like a messenger system to trigger hair follicle morphogenesis. Morphogenesis is the process in an organism where cells are organized into tissues and organs.
Over the past decades, scientists have explored crucial mechanisms related to hair follicle development using animal models. Since the complete understanding of these mechanisms of hair follicle development remains difficult, hair follicle morphogenesis has not been successfully reproduced in a culture dish in the laboratory.
More recently, organoid cultures have received wide attention. Organoids are tiny, simple versions of an organ – scientists produce them and use them to study the development and pathology of tissues and organs in a laboratory culture dish. “Organoids were a promising tool to elucidate the mechanisms of hair follicle morphogenesis in vitrosaid Tatsuto Kageyama, an assistant professor at the Yokohama National University School of Engineering.
The research team fabricated hair follicle organoids by controlling the structure generated from the two types of embryonic cells using a fairly low concentration of extracellular matrices. The extracellular matrix is the framework of the body that structures cells and tissues. The extracellular matrices adjusted the spacing between the two embryonic cell types from a dumbbell shape to a nucleus-shell configuration. Newly formed hair follicles with typical features emerged in core-shell shaped clusters. These core-shell clusters increase the area of contact between two cellular regions to enhance the mechanisms that contribute to hair follicle growth.
The organoid culture system developed by the research team generated hair follicles and hair shafts with almost 100% efficiency. Hair follicle organoids produced fully mature hair follicles with long hairs (about 3 mm in length over 23 days in culture). As this growth progressed, the researchers were able to monitor hair follicle morphogenesis and hair pigmentation. in vitro and understand the signaling pathways involved in the processes.
Researchers examined the feasibility of hair follicle organoids for drug screening and regenerative medicine. Next, they added a melanocyte-stimulating drug, which plays a key role in producing hair color pigmentation, to the culture medium. With the addition of this drug, researchers significantly improved the hair pigmentation of hair fibers. Moreover, by transplanting the hair follicle organoids, they achieved effective hair follicle regeneration with repeated hair cycles. They believe the in vitro The hair follicle model could prove useful to better understand hair follicle induction, to assess hair pigmentation and hair growth medications, and to regenerate hair follicles.
The researchers’ findings may also prove relevant to other organ systems and contribute to understanding the development of physiological and pathological processes. Looking ahead to future research, the team plans to optimize their organoid culture system with human cells. “Our next step is to use human-derived cells and apply for drug development and regenerative medicine,” said Junji Fukuda, a professor at the Yokohama National University School of Engineering.
Their future research could eventually open up new avenues of research for the development of new treatment strategies for hair loss disorders, such as androgenic alopecia which is common in both men and women.
The research team includes Tatsuto Kageyama of 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 from Yokohama National University; Yusuke Okubo, National Institute of Health Sciences; and Junji Fukuda, from Yokohama National University and Kanagawa Institute of Industrial Science and Technology.
Funding was provided by the Japan Science and Technology Agency; Ministry of Education, Culture, Sports, Science and Technology of Japan, Kanagawa Institute of Industrial Science and Technology, Japan Agency for Medical Research and Development, Sumitomo Foundation, the Hoya Science Foundation and the Kao Melanin Workshop.
Yokohama National University
Kageyama, T. et al. (2022) Reprogramming three-dimensional microenvironments for in vitro hair follicle induction. Scientific advances. doi.org/10.1126/sciadv.add4603.