Stem Cell-Based Therapy for Alopecia Areata: Mechanistic Rationale, Clinical Evidence, and Translational Barriers

• • AA has a cumulative lifetime incidence of 2% and can progress to AT/AU; conventional JAK inhibitors show breakthrough potential in severe AA but are limited by high recurrence rates after cessation, creating a clinical need for durable, disease-modifying alternatives. • • Stem cell-based therapy operates through four defined mechanisms—immunomodulation, oxidative stress mitigation, angiogenesis, and hair follicle cycle activation—with efficacy dependent on both delivery route and immunological context; systemic delivery may offer greater advantage in moderate-to-severe AA or AU. • • A time-dependent interaction between stem cell-based therapies and corticosteroids influences treatment outcomes, implying that combinatorial scheduling, not simple co-administration, determines response magnitude. • • Translation is blocked by the absence of standardized protocols for cell source, dosage, and delivery route, insufficient long-term safety data on genomic stability and tumorigenic risk, and the lack of large-scale randomized controlled trials comparing stem cell approaches with established JAK inhibitor therapy.