4.8 Article

Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction

Journal

SCIENCE ADVANCES
Volume 8, Issue 42, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.add4603

Keywords

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Funding

  1. Japan Science and Technology Agency (JST)PRESTO [JPMJPR19H2]
  2. Ministry of Education, Culture, Sports, Science, and Technology of Japan
  3. Sumitomo Foundation
  4. Hoyu Science Foundation
  5. Kao Melanin Workshop grant
  6. Kanagawa Institute of Industrial Science and Technology grant
  7. KAKENHI [18K18971, 19K21107, 20K20208, 20H02535]
  8. Japan Agency for Medical Research and Development [19213841]

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This study demonstrates the successful induction of hair follicle formation in vitro by controlling the interactions between epithelial and mesenchymal cells. The in vitro hair follicle model has potential applications in understanding hair follicle induction, evaluating drug effects on hair growth and inhibition, and modeling gray hairs.
During embryonic development, reciprocal interactions between epidermal and mesenchymal layers trigger hair follicle morphogenesis. This study revealed that microenvironmental reprogramming via control over these interactions enabled hair follicle induction in vitro. A key approach is to modulate spatial distributions of epithelial and mesenchymal cells in their spontaneous organization. The de novo hair follicles with typical morphological features emerged in aggregates of the two cell types, termed hair follicloids, and hair shafts sprouted with near 100% efficiency in vitro. The hair shaft length reached similar to 3 mm in culture. Typical trichogenic signaling pathways were up-regulated in hair follicloids. Owing to replication of hair follicle morphogenesis in vitro, melanosome production and transportation were also monitored in the hair bulb region. This in vitro hair follicle model might be valuable for better understanding hair follicle induction, evaluating hair growth and inhibition of hair growth by drugs, and modeling gray hairs in a well-defined environment.

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