lithium-chloride and Alopecia

Conventional therapeutic applications of mesenchymal stromal cells (MSCs) focus on cell replacement and differentiation; however, increasing evidence suggests that most of their therapeutic effects are carried out by their various secretions. This study investigated the application of conditioned medium (CM) from human umbilical cord blood-derived MSCs (hUCB-MSCs) to improve hair growth and developed a method to reliably produce this optimized CM. Primed MSC-derived CM (P-CM) with combinations of TGF-β1 and LiCl was optimized by comparing its effects on the cell viability of dermal papilla cells (DPCs). P-CM significantly increased the viability of DPCs compared to CM. The secretion of vascular endothelial growth factor (VEGF) in DPCs was regulated by the macrophage migration inhibitory factor (MIF) in the P-CM secreted by MSCs. These findings suggest that P-CM can improve the efficacy in hair growth via a paracrine mechanism and that MIF in P-CM exerts hair growth-promoting effects via a VEGF-related β-catenin and p-GSK-3β [SER9] signaling pathway. Furthermore, clinical trials have shown that 5% P-CM improved androgenetic alopecia through producing an increased hair density, thickness, and growth rate, suggesting that this topical agent may be a novel and effective treatment option for patients with androgenetic alopecia.

Topics: Adult; Alopecia; beta Catenin; Cell Survival; Cells, Cultured; Culture Media, Conditioned; Down-Regulation; Female; Fetal Blood; Glycogen Synthase Kinase 3 beta; Hair; Humans; Intercellular Signaling Peptides and Proteins; Lithium Chloride; Macrophage Migration-Inhibitory Factors; Mesenchymal Stem Cells; Middle Aged; Models, Biological; Transforming Growth Factor beta1; Up-Regulation; Vascular Endothelial Growth Factor A; Young Adult

Hair follicle (HF) regeneration begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. Wnt/β-catenin signalling is known to affect mammalian hair growth positively. In androgenetic alopecia (AGA), androgens cause HF miniaturization through a mechanism that remains unclear. Circulating androgens act on DPC and alter paracrine factors that influence hair epithelial cells.. To elucidate the role of androgens in dermal papilla-induced differentiation of HF stem cells.. HF stem cell differentiation was evaluated in a coculture model with DPC or culturing with media conditioned by DPC after activation of androgen and Wnt/β-catenin signalling pathways. To study the molecular cross-talk between the androgen and Wnt signalling pathway in DPC, we analysed the expression and activation of downstream Wnt signalling molecules in the presence of androgens.. In a coculture model with human DPC from patients with AGA and HF stem cells, we observed that androgens abrogate hair differentiation evaluated by hair-specific keratin 6 expression. Wnt signalling activation restored the ability of androgen-treated DPC to induce differentiation. Androgen treatment revealed a significant decrease in the cytoplasmic/total β-catenin protein ratio and upregulation of the activity of glycogen synthase kinase-3β in DPC, indicative of canonical Wnt pathway inhibition.. These results suggest that androgens deregulate DPC-secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway.

Topics: Alopecia; Androgens; Cell Differentiation; Cells, Cultured; Dermis; Dihydrotestosterone; DNA, Complementary; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hair Follicle; Humans; Keratins, Hair-Specific; Keratins, Type II; Lithium Chloride; Male; Real-Time Polymerase Chain Reaction; Receptors, Androgen; RNA; Scalp; Stem Cells; Transfection; Wnt Signaling Pathway