Hair follicle germs containing vascular endothelial cells for hair regenerative medicine

Tatsuto Kageyama,Junji Fukuda,Yang-Sook Chun

doi:10.1038/s41598-020-79722-z

Tatsuto Kageyama, Junji Fukuda + Show 1 more

Open Access

https://doi.org/10.1038/s41598-020-79722-z

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Abstract

Hair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss. Recent advances in three-dimensional tissue engineering, such as formation of hair follicle germs (HFGs), have considerably improved hair regeneration after transplantation in animal models. Here, we proposed an approach for fabricating HFGs containing vascular endothelial cells. Epithelial, dermal papilla, and vascular endothelial cells initially formed a single aggregate, which subsequently became a dumbbell-shaped HFG, wherein the vascular endothelial cells localized in the region of dermal papilla cells. The HFGs containing vascular endothelial cells exhibited higher expression of hair morphogenesis-related genes in vitro, along with higher levels of hair shaft regeneration upon transplantation to the dorsal side of nude mice, than those without vascular endothelial cells. The generated hair follicles represented functional characteristics, such as piloerection, as well as morphological characteristics comparable to those of natural hair shafts. This approach may provide a promising strategy for fabricating tissue grafts with higher hair inductivity for hair regenerative medicine.

Highlights

Hair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss
Prior to investigation with the three cell types, we examined whether the formation of hair follicle germs (HFGs) through self-sorting of epithelial and mesenchymal cells could occur even among cells from different species
Over the following two days of culture, the cells spatially separated within the individual aggregates and formed HFG-like structures, dermal papilla (DP) cells in larger aggregates, composed of > 8 × 103 cells/HFG, did not assemble into a single cluster and rather remained as a few clusters (Fig. 2a (ii))

Summary

Introduction

Hair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss. The generated hair follicles represented functional characteristics, such as piloerection, as well as morphological characteristics comparable to those of natural hair shafts This approach may provide a promising strategy for fabricating tissue grafts with higher hair inductivity for hair regenerative medicine. In vivo development of hair follicles is driven by the formation of hair follicle germs (HFGs) at a location between the epidermal and mesenchymal layers[3] Replication of such hair follicle development in vitro, including epithelial-mesenchymal interactions, has been considered to engineer tissue grafts for hair regenerative medicine[4,5,6]. The bioengineered HFGs efficiently regenerated hair follicles after transplantation in nude mice, which reassembled connections to host arrector pili and nerve fibers This approach could partially replicate in vivo hair follicle development. Involvement of vascular endothelial cells in HFGs may be beneficial for replicating hair follicle development and improving de novo hair follicle generation

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