Hair Follicle Regeneration Using Grafted Rodent and Human Cells

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.

Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis

“…6B), confirming the known requirement for dermal cells (Ehama et al, 2007). Conversely, when Sox2GFP dermis was engrafted without epithelial cells, a few hairs formed, indicating low-level contamination of dermal cells with epidermal cells (Fig.…”

“…Grafting studies were performed as previously described (Ehama et al, 2007), except for the following modifications. On the first day of the procedure, 6-mm diameter chambers (Renner, Dannstadt, Germany, Cat.…”

“…It is established and maintained through reciprocal signalling between the epithelium and a group of mesenchymal cells at the base of the follicle that constitute the dermal papilla (Ehama et al, 2007;Fuchs and Horsley, 2008;Horne and Jahoda, 1992;Jahoda, 1992;Muller-Rover et al, 2001;Paus et al, 1999;Watt and Hogan, 2000;Wu et al, 2004). Key signalling pathways that mediate the effects of the dermal papilla include the Wnt and BMP pathways (Kishimoto et al, 2000;Rendl et al, 2008;Shimizu and Morgan, 2004).…”

Knockout of p16INK4a promotes aggregative growth of dermal papilla cells

“…6 These observations confirm that low passages of cultured DPCs with aggregative growth not only have the ability to induce complete regeneration of hair follicles, but also carry the information needed to determine the nature of the hair, as corroborated by subsequent research. 7,8 It should be emphasized that the ability of DPCs to induce HF formation is dependent on their aggregative growth. But the mechanism by which the aggregative behavior disappears is not yet clear.…”

Environmental reprogramming and molecular profiling in reconstitution of human hair follicles

“…The most accessible source of human skin is neonatal foreskin. Early studies demonstrated that, although the foreskin epidermis is able to form HFs in combination with a murine DP, the foreskin dermis lacks the necessary cell populations or signals (24). Until recently, only fetal dermal and epidermal cells from the second trimester were known to generate hair follicles (18).…”