Impact of adipose-derived stem cells on engineering hair follicle germ-like tissue grafts for hair regenerative medicine.

Hair regenerative medicine has emerged as a promising treatment strategy for severe hair loss, such as end-stage androgenetic alopecia. Various approaches to engineering three-dimensional tissue grafts have been explored since they drive the ability to regenerate hair follicles when transplanted. In the present study, we demonstrated the assembly of human adipose-derived stem cells (hASCs) into hair follicle germ (HFG)-like aggregates for de novo hair regeneration. We mixed human dermal papilla cells (hDPCs), murine embryonic epithelial cells, and hASCs in suspension, and allowed them to form aggregates. During three days of culture, cells initially formed a single aggregate with a random distribution of the three cell types, but the epithelial and dermal papilla cells subsequently separated from each other and formed a dumbbell-shaped HFG, with hASCs localized on the hDPC aggregate side. The involvement of hASCs significantly increased gene expression associated with hair morphogenesis compared to HFGs without hASCs. The self-organization of the three cell types was observed in our scalable lab-made chip device. HFGs containing hASCs efficiently generated hair shafts upon transplantation to nude mice, while only a few shafts were generated with HFGs without hASCs. This approach may be a promising strategy for fabricating tissue grafts for hair regenerative medicine.