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Hair follicle germs containing vascular endothelial cells for hair regenerative medicine

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 the 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.1

Human DP cells, murine fetal skin-derived epithelial cells, and HUVECs were mixed and seeded in a non-cell-adhesive 96-well plate and lab-created HFG chip. In each culture vessel, the cells formed single aggregates in the microwells, wherein the three types of cells were randomly distributed after 1 day of culture and spontaneously formed vHFGs in the following 2 days of culture. vHFGs were then transplanted into the dorsal skin of nude mice to evaluate hair regeneration potential.
Preparation of vHFGs through self-organization.

1.Kageyama, T., Chun, YS. & Fukuda, J. Hair follicle germs containing vascular endothelial cells for hair regenerative medicine. Sci Rep11, 624 (2021).


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