<![CDATA[Background: Androgenetic alopecia (AGA) is the most common form of hair loss, characterized by progressive follicular miniaturization associated with dysregulation of suppressor of cytokine signaling 3 (SOCS3) and signal transducer and activator of transcription 3 (STAT3). Current therapies, such as minoxidil, provide limited efficacy and are often accompanied by side effects. Exosomes derived from hypoxia-conditioned mesenchymal stem cells (EH-MSCs) offer regenerative, immunomodulatory, and anti-inflammatory effects that may represent a novel therapeutic approach.Objective: To evaluate the therapeutic potential of EH-MSC exosomes in regulating SOCS3 and STAT3 signaling in a dihydrotestosterone-induced AGA mouse model.Methods: An in vivo randomized post-test–only control group design was conducted using thirty-four male C57BL/6 mice divided into five groups: healthy control (K1), DHT-induced AGA + saline (K2), DHT-induced + minoxidil 5% (K3), DHT-induced + EH-MSC exosomes 100 μg/kg (K4), and DHT-induced + EH-MSC exosomes 200 μg/kg (K5). Exosomes were isolated from hypoxia-preconditioned umbilical cord MSCs using tangential flow filtration and validated with CD63/CD9 markers by flow cytometry. SOCS3 and STAT3 expression levels were analyzed by qRT-PCR. Statistical tests included Shapiro–Wilk, Levene’s, one-way ANOVA, and post hoc analysis.Results: EH-MSC exosomes significantly modulated SOCS3 and STAT3 expression in a dose-dependent manner. The high-dose EH-MSC group (K5) restored SOCS3 expression (1.25 ± 0.18 pg/mL) to levels comparable with healthy controls (1.00 ± 0.00 pg/mL) and suppressed STAT3 expression (0.89 ± 0.15 pg/mL) toward normal values. Minoxidil only partially improved SOCS3 (0.49 ± 0.16 pg/mL) and STAT3 (2.32 ± 0.19 pg/mL) expression compared to untreated AGA controls.Conclusion: Exosomes derived from hypoxia-preconditioned MSCs demonstrated superior immunomodulatory effects compared to minoxidil by enhancing SOCS3 and suppressing STAT3 expression, thereby restoring follicular homeostasis in AGA. These findings suggest EH-MSC exosomes as a promising exosome-based therapeutic strategy for androgenetic alopecia, with potential implications for clinical nursing practice in regenerative dermatology.]]>
