Effect of platelet-rich plasma in refractory vitiligo by promoting the differentiation of dermal melanocyte progenitors via IGFBP-2/RhoA/YAP pathway

• PRP combined with 308-nm excimer phototherapy improves repigmentation in acral vitiligo related to dermal melanocyte progenitors’ activation. • The differentiation trajectory from dermal melanocyte progenitors to functional melanocytes was established and validated. • PRP significantly enhances the differentiation of dermal melanocyte progenitors into melanocytes in glabrous skin organoid model. • IGFBP-2 as a key effector in PRP that promotes melanocyte differentiation via the IGFBP-2/RhoA/YAP signaling axis. • Dermal melanocyte progenitors represent a promising, follicle-independent source for melanocyte regeneration in acral vitiligo. Vitiligo is an acquired depigmenting disorder. Current repigmentation strategies aim to prevent melanocyte loss and promote regeneration, often by enhancing the differentiation of melanocyte progenitors. However, acral vitiligo, lacking hair follicles, exhibits poor therapeutic response. Platelet-rich plasma (PRP) may offer an alternative approach, but its effects on dermal melanocyte progenitors (DMPs) remain unclear. To evaluate the therapeutic effect and mechanisms of PRP and 308-nm excimer phototherapy in refractory vitiligo. We conducted a single-center, prospective, randomized split-body clinical observation (n = 30, with 20 split-body and 10 PRP-only) to assess the effectiveness of PRP combined with 308-nm excimer phototherapy in patients with stable acral vitiligo over a 5-month treatment duration. A defined induction system was established to generate functional melanocytes. Bulk and single-cell RNA sequencing analyzed phenotypic changes. A glabrous skin organoid model was established to study acral melanocyte regeneration and assess PRP’s effects. Protein microarray was used to identify key effectors in PRP. Clinically, PRP combined with phototherapy significantly improved repigmentation in acral vitiligo, presenting a diffuse pattern on the palms and distal fingers. Pigment index improvements in the PRP + 308 vs. NS + 308 groups were observed on the dorsum (44.30 ± 6.17 vs 36.40 ± 4.94), palms (20.15 ± 3.10 vs 16.45 ± 4.73), proximal fingers (31.75 ± 3.73 vs 29.00 ± 3.52), and distal fingers (19.90 ± 3.88 vs 19.45 ± 3.80). Palm repigmentation correlated with the activation of DMPs. In vitro and in vivo transcriptomic analyses demonstrated a defined differentiation trajectory from DMPs to melanocytes. In both cell-based and glabrous skin organoid models, PRP promotes melanocyte differentiation. IGFBP-2 was identified as a key effector in PRP through the IGFBP-2/RhoA/YAP signaling axis. PRP renders additional clinical benefits in the treatment of acral vitiligo through activation of the IGFBP-2/RhoA/YAP signaling to drive DMP-to-melanocyte differentiation. This establishes DMPs as a novel, follicle-independent melanocyte source and supports a promising therapeutic strategy for treatment-resistant vitiligo.