TGF‐β₂ is specifically expressed in human dermal papilla cells and modulates hair folliculogenesis

Abstract

Dermal papilla cells (DPCs) in the mammalian hair follicle have been shown to develop hair follicles through epithelial–mesenchymal interactions. A cell therapy to regenerate human hair is theoretically possible by expanding autologous human DPCs (hDPCs) and transplanting them into bald skin, though much remains to be overcome before clinical success. In this study, we compared gene signatures of hDPCs at different passages and human dermal fibroblasts, and found transforming growth factor (TGF)-β2 to be highly expressed in cultured hDPCs. Keratinocyte conditioned medium, which is known to help preserve the hair-inducing capacity of hDPCs, up-regulated TGF-β2 expression of hDPCs and also enhanced their alkaline phosphatase (ALP) activity, a known index for hair-inductive capacity. Through screening of components secreted from keratinocytes, the vitamin D3 analogue was found to promote TGF-β2 expression and ALP activity of hDPCs. In animal hair folliculogenesis models using rat epidermis and expanded hDPCs, inhibition of TGF-β2 signalling at the ligand or receptor level significantly impaired hair folliculogenesis and maturation. These results suggest an important role for TGF-β2 in hair follicle morphogenesis and provide insights into the establishment of future cell therapies for hair regrowth by transplanting expanded DPCs.

1α,25-Dihydroxyvitamin D3 Modulates the Hair-Inductive Capacity of Dermal Papilla Cells: Therapeutic Potential for Hair Regeneration

“…1A). Likewise, gene expression of ALPL and TGF-␤2, both related to the hair-inductive capacity of hDPCs [24], was upregulated by VD 3 treatment at 24 -48 hours (supplemental online Fig. 1B, 1C).…”

“…The dermal papilla and lower dermal sheath around the end bulb of a follicle specifically express ALP activity and have the potential capacity to restore hair growth [25]. TGF-␤2 is involved in promotion of the hair placode [16], contributes to anagen induction [45], is highly expressed in hDPCs compared with hDFs, and is suggested to mediate the hair-inductive capacity of DPCs [24]. Wnt10b is known to play crucial roles in fetal development of hair follicles.…”

“…We also found that among paracrine factors from keratinocytes, 1␣,25-dihydroxyvitamin D 3 (VD 3 ; also known as calcitriol) upregulated TGF-␤2 gene expression in hDPCs. VD 3 , likewise, upregulated alkaline phosphatase (ALP) activity [24], which is used as an index for the hair-inductive capacity of DPCs [14,25,26].…”

Conditioned media obtained from human outer root sheath follicular keratinocyte culture activates signalling pathways that contribute to maintenance of hair‐inducing capacity and increases trichogenicity of cultured dermal cells

“…In addition, Qiao et al (5) recently demonstrated maintenance of trichogenicity of cultured human DP cells cultured in medium conditioned with keratinocytes of newborn foreskin. In addition, Inoue et al (6) reported that use of conditioned media obtained from culture of human facial skin keratinocytes resulted in preservation of the trichogenicity of human DP cells.…”

Fundamental hair follicle biology and fine fibre production in animals

“…Deficiency symptoms have been described for inadequacy of vitamin supply, which relate to generally well-understood roles in cell biochemistry. These include ribloflavin, niacin, pantothenic acid, folic acid and biotin (general effects on integumental tissues including caprine and sheep hair follicles (Tahmasbi et al, 2007a and2007b;Galbraith 2010)), vitamin A and retinoids, which are essential for cell proliferation and vitamin D that influences TGF b2 upregulation and follicle development (Inoue et al, 2009). Important cations include calcium that provides signal transduction in keratinocytes (Pruche et al, 1996) and magnesium, which has a role in energy-providing phosphate transfer reactions and DNA degradation and synthesis.…”