Expansion and characterization of epithelial stem cells with potential for cyclical hair regeneration.

Affiliation

Takeo M(#)(1), Asakawa K(#)(1), Toyoshima KE(1)(2), Ogawa M(1)(2), Tong J(3), Irié T(4), Yanagisawa M(5), Sato A(6), Tsuji T(7)(8)(9)(10)(11).
Author information:
(1)Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology
(CDB) and RIKEN Center for Biosystems Dynamics Research
(BDR), Hyogo, 650-0047, Japan.
(2)Organ Technologies Inc., Tokyo, 101-0048, Japan.
(3)Department of Bioscience, Graduate School of Science and Technology, Kwansei-Gakuin University, Hyogo, 669-1337, Japan.
(4)Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, Iwate, 028-3694, Japan.
(5)Department of Plastic and Aesthetic Surgery, School of Medicine, Kitasato University, Kanagawa, 252-0375, Japan.
(6)Department of Plastic and Reconstructive Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
(7)Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology
(CDB) and RIKEN Center for Biosystems Dynamics Research
(BDR), Hyogo, 650-0047, Japan. [Email]
(8)Organ Technologies Inc., Tokyo, 101-0048, Japan. [Email]
(9)Department of Bioscience, Graduate School of Science and Technology, Kwansei-Gakuin University, Hyogo, 669-1337, Japan. [Email]
(10)Department of Plastic and Aesthetic Surgery, School of Medicine, Kitasato University, Kanagawa, 252-0375, Japan. [Email]
(11)Department of Plastic and Reconstructive Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan. [Email]
(#)Contributed equally

Abstract

In mammals, organ induction occurs only during embryonic development except for hair follicles (HFs). However, HF-resident epithelial stem cells (HFSCs), which are responsible for repetitive HF regeneration, are not fully characterized. Here, we establish in vitro culture systems that are capable of controlling the ability of HFSCs to regenerate HFs. Based on a method that precisely controlled the number of HFs for regeneration, functional analysis revealed that CD34/CD49f/integrin β5 (Itgβ5)-triple-positive (CD34+/CD49f+/Itgβ5+) cells have multipotency and functional significance for continual hair regeneration. In native HFs, these cells reside in the uppermost area of the bulge region, which is surrounded by tenascin in mice and humans. This study unveils the subpopulation of HFSCs responsible for long-term hair cycling of HFs regenerated from bioengineered HF germ, suggesting the presence of functional heterogeneity among bulge HFSCs and the utility of our culture system to achieve HF regenerative therapy.