Human umbilical cord-mesenchymal stem cells conditioned medium attenuates CCl₄ induced chronic liver fibrosis

Abstract

Although the efficacy of MSCs on the liver fibrosis is investigated, it is not exactly clear whether released molecules by MSCs are sufficient to mediate the anti-fibrotic effects or not. In this study, the possible hepatoprotective effects of human umbilical cord MSCs derived conditioned medium (UC-CM) was investigated. 30 male rats were divided into 3 groups (n = 10): C: control; F: fibrosis were intraperitoneally injected with CCl₄ (1 ml/kg, i.p); F/UC-CM: fibrosis rats that received UC-CM (100 µg/kg, i.v). At the end of the 12th week, serum and liver samples were collected to analyze biochemical, molecular, and histopathological parameters. In comparison with CCl₄ intoxicated animals, the results showed a significant amelioration of weight loss, histological changes as well as attenuation of serum activity of ALT, AST, and ALP in F/UC-CM. The liver hydroxyproline content was significantly reduced by UC-CM treatment. Accordingly, improvement in oxidative parameters such as MDA, TAC, and TOS was also observed in the F/UC-CM group. UC-CM administration down-regulated gene expression of TGF-β1, TNF-α, TβRII, MMP-2, and MMP-9 as well as the protein level in TGF-β1 and TNF-α. Immunohistochemical analysis showed a notable lower hepatic α-SMA expression in the F/UC-CM group. In conclusion, these findings revealed that the remarkable hepatoprotective property of UC-CM could lend support to its anti-inflammatory and antioxidative and anti-fibrotic effects.

Keywords:

• Liver fibrosis
• transforming growth factor beta1
• tumor necrosis factor-alpha
• smooth muscle actin
• conditioned medium

Disclosure statement

No conflict of interest is declared by the authors.

Additional information

Funding

Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences [No. 9504221985].