Hair follicle bulge-derived stem cells promote tissue regeneration during skin expansion

Skin expansion is widely used in reconstructive surgery to obtain supplemental and optimal skin. Enhancing the regenerative capacity of expanded skin is therefore of great interest. Hair follicle bulge-derived stem cells (HFBSCs) located in hair follicle bulges are closely associated with skin; HFBSC transplantation could promote cutaneous wound repair. However, the effects of transplanted HFBSCs on skin regeneration during expansion remain unclear. The aim of the study was to reveal the potential effects of transplanted HFBSCs in the expanded skin and explore its mechanism. Our results showed higher skin area, tissue weight, epidermal thickness, dermal thickness, proliferating cell count, collagen content, microcirculatory blood flow, blood vessels, and lower retraction ratios were observed in HFBSC-injected rats compared to uninjected controls. Moreover, the transplanted HFBSCs directly contributed to tissue regeneration by differentiating into vascular endothelial cells, epidermal cells, and the outer root sheath cells of hair follicle. Higher expression of EGF, VEGF, bFGF, and TGF-β were observed in HFBSC-injected rats. Our research demonstrated the transplanted HFBSCs could promote skin regeneration by differentiating into various types of skin related cells and by up-regulating the expression of growth factors. Our results could form a basis for the development of novel strategies to enhance regeneration in expanded skin by using HFBSCs.