Cross-Signaling Between Hair Follicle Stem Cells And Dermal Lymphatic Vessels: A Systematic Review

PURPOSE: Hair follicle stem cells (HFSCs) reside in a niche rich with blood and lymphatic vessels and have been demonstrated to facilitate wound healing. However, specific interactions between HFSCs and dermal lymphatic vessels remain poorly understood. We conducted a systematic review to investigate signaling interactions between HFSCs and lymphatic vessels to determine future therapeutic targets for wound healing and hair loss disorders. METHODS: A systematic literature review in accordance with PRISMA guidelines was conducted in September 2025 using PubMed/MEDLINE, Web of Science, and Cochrane databases. Skin immunohistochemical studies conducted in humans or mice that characterize interactions of HFSCs and dermal lymphatic vessels were included for review. RESULTS: Ten articles were included for review, with nine studies conducted in murine models and one study conducted in human scalp tissue samples. HFSC - lymphatic vessel cross-signaling is dynamic and changes throughout the hair cycle. At the onset of HFSC activation (anagen phase), lymphatic vessels transiently dilate and increase fluid drainage, accompanied by distinct changes in lymphatic endothelial cell (LEC) gene expression. In the quiescent (telogen) phase, HFSCs secrete Angptl7 to maintain lymphatic engagement and drainage. LECs also exert paracrine signaling on HFSCs. LECs stimulate HFSC growth with secretion of growth signals including IGF-1 and Sostdc1 that activate Wnt signaling to promoting hair follicle growth. Several studies modulated dermal LEC growth to determine impacts to HFSC growth. Augmented lymphangiogenesis prolonged the hair growth phase while LEC depletion or LEC signaling blockade led to premature hair follicle regression or failure of hair follicle regeneration. One human scalp study demonstrated that aging and alopecia were associated with diminished lymphatic vessel networks in the skin. CONCLUSION: This systematic review identifies that cutaneous lymphatic vessels are a critical component of the HFSC niche, coordinating hair follicle growth and tissue regeneration. Included studies highlight the bidirectional cross-signaling between HFSCs and LECs: HFSCs actively remodel lymphatic vessels, and LECs reciprocally secrete factors that support hair follicle growth. Disruption to HFSC-lymphatic interactions dysregulates the hair growth cycle, while enhancing lymphatic function improves hair follicle growth. HFSC-lymphatic signaling pathways may represent a novel target for therapeutics to promote wound healing and treat hair loss disorders. *Source: https://ps-rc.org/meeting/Program/2026/128.cgi*