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

Abstract

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.

Hypoxia improves hair inductivity of dermal papilla cells via nuclearNADPHoxidase 4‐mediated reactive oxygen species generation'

“…1 HFs are composed of keratinocytes and a specialized mesenchymal population, dermal papilla cells (DPCs). 2,3 Reduced generation of HFs results in progressive hair thinning/loss, and is associated with a failure to maintain DPC number, which specifies hair size, shape and cycling. 4 The dermal papilla (DP), a spheroid structure at the base of the HF, comprises specialized fibroblasts derived from the dermal mesenchyme.…”

Advances of Stem Cell Therapeutics in Cutaneous Wound Healing and Regeneration

“…The unique reprogramming of iPSC technology made it possible to generate genetically diverse patient-specific cell lines from genetic skin disorders or chronic wounds which have tremendous potential for disease modeling and drug screening [ 59 , 60 ]. During the last decade, significant progress has been made in the differentiation of the mouse, human iPSCs in to dermal stem cells and hair follicle lineages [ 58 , 61 ], mesenchymal cells with the potential of forming dermal papilla [ 62 ], fibroblasts [ 63 ], melanocytes [ 64 ], keratinocytes [ 65 , 66 ], among others. The multipotent capacity with limited immunoreactivity of iPSCs makes them a prospective agent for treating chronic skin disorders and unresolved wounds [ 67 ].…”

Generation of trichogenic adipose-derived stem cells by expression of three factors

“…They showed DP cells endogenously express high levels of Sox2 and c-Myc, and that these cells can be reprogrammed into iPS cells with only Oct4 and Klf4 [37]. On the contrary, Ohyama's group differentiated ectoderm precursor cells (EPCs), DP-like cells, and mesenchymal stem cells (MSCs) using iPS cells [38][39][40]. For example, EPCs were generated with 4 or 3 factors (POU5F1, SOX2, KLF4 +/-MYC), and mostly expressed keratin 18, a marker of epithelial progenitors [40].…”

“…For example, EPCs were generated with 4 or 3 factors (POU5F1, SOX2, KLF4 +/-MYC), and mostly expressed keratin 18, a marker of epithelial progenitors [40]. Of interest, a highly proliferative and plastic LNGFR(+)THY-1(+) subset of iPS cell-generated MSCs was subsequently programmed using retinoic acid and DP culture medium to acquire DP properties [38,39]. In the present study, we overexpressed PDGF-A, Sox2, and -catenin into ASCs, replaced the culture media with DP culture media, and characterized the DP properties of tfASCs.…”