Eko Setiawan
Department of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang

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Hypoxia-Conditioned MSC Exosomes Upregulate mTORC1 and Suppress MMP-2 in a UV-B–Induced Collagen Loss Rat Model Anggrila Sekar Fadhillah; Agung Putra; Titiek Sumarawati; Eko Setiawan
Molecular and Cellular Biomedical Sciences Vol 10, No 1 (2026)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v10i1.749

Abstract

Background: Ultraviolet-B (UV-B) radiation accelerates photoaging by disrupting extracellular matrix (ECM) homeostasis through dysregulation of mechanistic target of rapamycin complex 1 (mTORC1) and upregulation of matrix metalloproteinase-2 (MMP-2). This study evaluated the effects of exosomes of hypoxia-conditioned mesenchymal stem cells (EH-MSCs) on mTORC1 and MMP-2 expression in a UV-B–induced collagen loss rat model.Materials and Methods: Thirty male Wistar rats were randomized into five groups: healthy control, UV-B + saline, UV-B + hyaluronic acid, UV-B + 200 µL EH-MSCs, and UV-B + 300 µL EH-MSCs. Collagen loss was induced by UV-B irradiation for two weeks (10 sessions, 8 min/session). A single treatment was administered on day 22, and tissue was collected on day 29. Exosomes were isolated from hypoxia-conditioned MSCs and characterized by morphology and surface markers. Gene expression of mTORC1 and MMP-2 was assessed by qRT-PCR and analyzed using one-way ANOVA.Results: UV-B exposure induced collagen loss histologically. EH-MSCs significantly increased mTORC1 expression, highest in the 300 µL group (p < 0.001), and reduced MMP-2 expression, lowest in the 300 µL group.Conclusion: EH-MSCs exert dual regulatory effects by upregulating mTORC1 and suppressing MMP-2 in UV-B–induced collagen loss, suggesting therapeutic potential to mitigate photoaging via anabolic signaling (via mTORC1) and reduced ECM degradation (via MMP-2).Keywords: collagen loss, exosomes, MMP-2, mTORC1, UV-B
Hypoxia-Derived Mesenchymal Stem Cell Exosomes Downregulate CXCL12 and Upregulate IL-10 Expression in a Murine Model of Androgenic Alopecia Denawati Denawati; Eko Setiawan; Sri Priyantini
Molecular and Cellular Biomedical Sciences Vol 10, No 1 (2026)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v10i1.745

Abstract

Background: Androgenic alopecia (AGA) is characterized by hair follicle miniaturization and chronic inflammation mediated by dihydrotestosterone (DHT). Current therapies primarily target hormonal pathways and do not adequately address inflammatory dysregulation. Exosomes derived from hypoxia-conditioned mesenchymal stem cells (EH-MSCs) exhibit enhanced immunomodulatory properties. However, their effects on key inflammatory mediators in AGA remain unclear. This study evaluated the effects of EH-MSCs on CXCL12 and IL-10 expression in a DHT-induced AGA mouse model.Materials and methods: Male C57BL/6 mice were allocated into five groups: healthy control, DHT-induced alopecia without treatment, DHT-induced alopecia treated with topical minoxidil, and EH-MSCs administered at 100 or 200 µL/kgBW. Alopecia was induced by subcutaneous DHT injection for 17 days. Following model validation, treatments were administered on days 25 and 32. CXCL12 and IL-10 expression in dorsal skin tissue was analyzed using RT-PCR on day 39.Results: DHT induction significantly increased CXCL12 expression and reduced IL-10 levels (p<0.05). EH-MSC administration dose-dependently downregulated CXCL12 (1.73±0.57 and 1.54±0.44 fold-change) and upregulated IL-10 expression (3.10±0.75 and 3.29±0.67 fold-change), demonstrating greater immunomodulatory effects compared with minoxidil.Conclusion: EH-MSCs effectively modulated inflammatory biomarkers by suppressing CXCL12 and enhancing IL-10 expression in a DHT-induced AGA model, suggesting their potential as an immunoregenerative therapeutic strategy for androgenic alopecia.Keywords: androgenic alopecia, mesenchymal stem cells, exosomes, hypoxia, CXCL12, IL-10