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

Articles in Press

Document Type : Original Article

Authors

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

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

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

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

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

8 Faculty of Pharmacy, Universitas Jenderal Achmad Yani, Cimahi 40531, West Java, Indonesia

9 Department of Zoology and Research Centre, Lady Doak College Madurai, India

10 Department of Physiology, Biochemistry, and Pharmacology; College of Veterinary Medicine, University of Kirkuk, Kirkuk 36001, Iraq

10.22038/ijbms.2026.93115.20079

Abstract

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.  

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References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 10 May 2026

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