Hypoxia-Mesenchymal Stem Cell Exosomes As A Novel Therapy Targeting Socs3/Stat3 Signaling In Androgenic Alopecia

Pinandhito Nararya Wirrya Latukolan (Department of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang)
Eko Setiawan (1. Department of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang 2. Department of Surgery, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang)
Sri Priyantini (Department of Pediatrics, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang)

Journal of Biomedicine and Translational Research
Vol 12, No 2 (2026): August 2026

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.