Functional hair follicle regeneration: an updated review

Abstract

The hair follicle (HF) is a highly conserved sensory organ associated with the immune response against pathogens, thermoregulation, sebum production, angiogenesis, neurogenesis and wound healing. Although recent advances in lineage-tracing techniques and the ability to profile gene expression in small populations of cells have increased the understanding of how stem cells operate during hair growth and regeneration, the construction of functional follicles with cycling activity is still a great challenge for the hair research field and for translational and clinical applications. Given that hair formation and cycling rely on tightly coordinated epithelial-mesenchymal interactions, we thus review potential cell sources with HF-inducive capacities and summarize current bioengineering strategies for HF regeneration with functional restoration.

Fig. 1

The process of hair cycling and DPCs in HF regeneration. a Mature and actively growing HFs anchored in the subcutis periodically regenerate by spontaneously undergoing anagen (repetitive cycles of growth), catagen (apoptosis-driven regression) and telogen (relative quiescence), which is termed hair cycling and is a typical characteristic of functional HFs. b Skeleton diagram of potential cells that contribute to regenerating HFs. c iPSCs share similar characteristics with embryonic stem cells in terms of morphology, self-renewal and differentiation capacity, and they can be induced into other potential cells in regenerative medicine. The transformation of fibroblasts into DPCs via lineage reprogramming. Optimization of the in vitro system to preserve the HF-inducive potential and the transplantation of cell-based biomaterials or HF organoids in vivo to regenerate HFs

Fig. 2

Keratinocytes and SKPs in HF regeneration. a iPSCs were reprogrammed into keratinocytes, and biomaterials containing a mixture of fibroblasts and keratinocytes were embedded for de novo HF. b Fibroblasts were chemically induced into SKPs. A mixture of SKPs and epidermal stem cells or bioactive peptides was embedded in the hydrogel to regenerate HFs three-dimensionally

Fig. 3

Strategies to achieve functional HF regeneration

Fig. 4

The regulatory factors of DPC HF-inducive capacity. Glucose metabolism and LncRNA-XIST/miR-424 axis in the regulation of HF-inducive potential of DP spheres