Hair follicle germs containing vascular endothelial cells for hair regenerative medicine

waynakyo

Experienced Member
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464
Did I miss this one? Jan 2021
open access: https://www.nature.com/articles/s41598-020-79722-z

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.


Murine embryonic cells generally exhibit a strong ability to regenerate hair follicles de novo. However, the regenerative ability of adult human hair follicle stem cells often deteriorates even when the same approach is used10. Thus, further studies using human cells would be necessary to better replicate in vivo development and hair follicle microenvironment for clinical applications. Perivascular microenvironments are essential for the development and maintenance of stem cells in many tissues. During development, newly forming vessels approach the nascent follicles, and the vascular annulus is completely developed by birth11. Reconstituted hair follicles spontaneously form vascular loops around the upper bulge, recapitulating the pattern of normal hair-bearing skin11. Furthermore, hair growth and hair follicle size significantly correlate with perifollicular angiogenesis induced by vascular endothelial growth factor12. Thus, involvement of vascular endothelial cells in HFGs may be beneficial for replicating hair follicle development and improving de novo hair follicle generation.

This study aimed to determine whether vascular endothelial cells participate in the self-organization of HFGs and improve hair regeneration. We added human vascular endothelial cells to a suspension of human dermal papilla (DP) and mouse embryonic epithelial cells and allowed them to form an aggregate in a 96-well plate and custom-designed microwell array plate (Fig. 1). Localization of vascular endothelial cells in an HFG and their effects on follicular gene expression were assessed. Furthermore, we investigated the effects of vascular endothelial cells on hair regeneration in animal models. Our findings provided insight into in vitro self-organization and in vivo morphogenesis of hair follicles, thus providing a promising strategy for hair regenerative medicine.
 
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