1. ¹Life Science Research Center, Shiseido Research Center, Yokohama, Japan
2. ²HAB Research Organization, Ichikawa, Chiba, Japan
3. ³Department of Dermatology, Ehime University School of Medicine, Ehime, Japan

Correspondence: Dr Jiro Kishimoto, Life Science Research Center, Shiseido Research Center, 2-2-1 Hayabuchi, Tsuzuki, Yokohama, Kanagawa 224-8558, Japan. E-mail: jiro.kishimoto@to.shiseido.co.jp

Received 20 October 2005; Revised 6 February 2007; Accepted 13 February 2007; Published online 12 April 2007.

Abstract

Hair follicle regeneration involves epithelial–mesenchymal interactions (EMIs) of follicular epithelial and dermal papilla (DP) cells. Co-grafting of those cellular components from mice allows complete hair reconstitution. However, regeneration of human hair in a similar manner has not been reported. Here, we investigated the possibility of cell-based hair generation from human cells. We found that DP-enriched cells (DPE) are more critical than epidermal cells in murine hair reconstitution on a cell number basis, and that murine DPE are also competent for hair regeneration with rat epidermal cells. Co-grafting of human keratinocytes derived from neonatal foreskins with murine DPE produced hair follicle-like structures consisting of multiple epidermal cell layers with a well-keratinized innermost region. Those structures expressed hair follicle-specific markers including hair keratin, and markers expressed during developmental stages. However, the lack of regular hair structures indicates abnormal folliculogenesis. Similar hair follicle-like structures were also generated with cultured human keratinocytes after the first passage, or with keratinocytes derived from adult foreskins, demonstrating that epidermal cells even at a mature stage can differentiate in response to inductive signals from DP cells. This study emphasizes the importance of EMI in follicular generation and the differentiation potential of epidermal keratinocytes.