Iranian journal of basic medical sciences · 2026
Hepatoprotective effect of hUC-MSC secretome in LPS-induced HepG2 cells.
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Widowati Wahyu, Onggowidjaja Philips, Vosough Massoud, Triharsiwi Dwi Nur, Distya Anindita Putri, Nurani Lisna Wahyu, Rahmawati Ismia, Aryani Any, Priyandoko Didik, Azis Rizal, Hadiprasetyo Dhanar Septyawan, Rajendran Priyatharsini, Abass Kasim Sakran, Rifana Safira Dinda
Аннотация
OBJECTIVES: This study aimed to evaluate the cytotoxicity and hepatoprotective effects of human umbilical cord mesenchymal stem cell-derived secretome (hUCMSC-Sec) in lipopolysaccharide (LPS)-induced HepG2 cells as an in vitro model of liver inflammation.
MATERIALS AND METHODS: hUCMSC-Sec was obtained from conditioned media of hUCMSCs at passage four. Inflammation was induced in HepG2 cells using LPS. Cytotoxicity was assessed using the WST-8 assay. Hepatoprotective effects of hUCMSC-Sec at concentrations of 12.5%, 4.17%, and 1.39% were evaluated by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and tumor necrosis factor-alpha (TNF-α). Gene expression levels of α-smooth muscle actin (α-SMA), SMAD-7, collagen type I alpha 1 (COL1A1), and matrix metalloproteinase-1 (MMP-1) were analyzed using quantitative real-time PCR.
RESULTS: hUCMSC-Sec concentrations ranging from 1.6% to 25% were non-toxic, maintaining cell viability above 90%. Treatment with hUCMSC-Sec significantly reduced ALT, AST, GGT, and TNF-α levels in LPS-induced HepG2 cells. In addition, hUCMSC-Sec down-regulated α-SMA, COL1A1, and MMP-1 expression, while up-regulating SMAD-7 expression. The concentration of 4.17% showed the most pronounced hepatoprotective effect.
CONCLUSION: hUCMSC-derived secretome demonstrated hepatoprotective effects by attenuating inflammatory and fibrotic responses in LPS-induced HepG2 cells. However, as this study was limited to an in vitro model, further in vivo and clinical studies are required to confirm its therapeutic potential and translational applicability.
MATERIALS AND METHODS: hUCMSC-Sec was obtained from conditioned media of hUCMSCs at passage four. Inflammation was induced in HepG2 cells using LPS. Cytotoxicity was assessed using the WST-8 assay. Hepatoprotective effects of hUCMSC-Sec at concentrations of 12.5%, 4.17%, and 1.39% were evaluated by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and tumor necrosis factor-alpha (TNF-α). Gene expression levels of α-smooth muscle actin (α-SMA), SMAD-7, collagen type I alpha 1 (COL1A1), and matrix metalloproteinase-1 (MMP-1) were analyzed using quantitative real-time PCR.
RESULTS: hUCMSC-Sec concentrations ranging from 1.6% to 25% were non-toxic, maintaining cell viability above 90%. Treatment with hUCMSC-Sec significantly reduced ALT, AST, GGT, and TNF-α levels in LPS-induced HepG2 cells. In addition, hUCMSC-Sec down-regulated α-SMA, COL1A1, and MMP-1 expression, while up-regulating SMAD-7 expression. The concentration of 4.17% showed the most pronounced hepatoprotective effect.
CONCLUSION: hUCMSC-derived secretome demonstrated hepatoprotective effects by attenuating inflammatory and fibrotic responses in LPS-induced HepG2 cells. However, as this study was limited to an in vitro model, further in vivo and clinical studies are required to confirm its therapeutic potential and translational applicability.