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Sci Rep. 2017 Feb 21;7:42777. doi: 10.1038/srep42777.

Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY-1(+) mesenchymal cells.

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Department of Dermatology, Keio University School of Medicine 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Physiology, Keio University School of Medicine 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Laboratory of Tumor Biology, Department of Life Sciences, Faculty of Medicine, Shimane University, Shiojicho 89-1, Izumo-shi, Shimane, 693-8501, Japan.
KOSÉ Endowed Program for Skin Care and Allergy Prevention, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Dermatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, Japan.


The dermal papilla (DP) is a specialised mesenchymal component of the hair follicle (HF) that plays key roles in HF morphogenesis and regeneration. Current technical difficulties in preparing trichogenic human DP cells could be overcome by the use of highly proliferative and plastic human induced pluripotent stem cells (hiPSCs). In this study, hiPSCs were differentiated into induced mesenchymal cells (iMCs) with a bone marrow stromal cell phenotype. A highly proliferative and plastic LNGFR(+)THY-1(+) subset of iMCs was subsequently programmed using retinoic acid and DP cell activating culture medium to acquire DP properties. The resultant cells (induced DP-substituting cells [iDPSCs]) exhibited up-regulated DP markers, interacted with human keratinocytes to up-regulate HF related genes, and when co-grafted with human keratinocytes in vivo gave rise to fibre structures with a hair cuticle-like coat resembling the hair shaft, as confirmed by scanning electron microscope analysis. Furthermore, iDPSCs responded to the clinically used hair growth reagent, minoxidil sulfate, to up-regulate DP genes, further supporting that they were capable of, at least in part, reproducing DP properties. Thus, LNGFR(+)THY-1(+) iMCs may provide material for HF bioengineering and drug screening for hair diseases.

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