Hepatoprotective effect of hUC-MSC secretome in LPS-induced HepG2 cells

نویسندگان

1 Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia

2 Molecular Medicine Department, Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran

3 Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163 West Java, Indonesia

4 Departement of Biology, Faculty of Mathematics and Natural Science Universitas Pendidikan Indonesia, Bandung 40154, West Java, Indonesia

5 Departement of Biology, Faculty of Mathematics and Natural Science Universitas Pendidikan Indonesia, Bandung 40154, West Java, Indonesia

6 Departement of Biology, Faculty of Mathematics and Natural Science Universitas Pendidikan Indonesia, Bandung 40154, West Java, Indonesia

7 Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia

8 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Tehran, Iran

9 Experimental Cancer Medicine, Institution for Laboratory Medicine, and Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden

10 Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163 West Java, Indonesia

11 Departement of Biology, Faculty of Mathematics and Natural Science Universitas Pendidikan Indonesia, Bandung 40154, West Java, Indonesia

12 Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163 West Java, Indonesia

13 Biomedical Engineering, Department of Electrical Engineering, Faculty of Engineering, Universitas Indonesia, Depok 16425, West Java, Indonesia

14 Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163 West Java, Indonesia

doi
10.22038/ijbms.2026.93115.20079
چکیده

Objective(s): 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.