Fucoxanthin Enhances the Antifibrotic Potential of Placenta-derived Mesenchymal Stem Cells in a CCl4-induced Mouse Model of Liver Fibrosis

Vasilii Slautin; Konstantin Konyshev; Ilya Gavrilov; Olga Beresneva; Irina Maklakova; Dmitry Grebnev

doi:10.2174/011574888X279940231206100902

Fucoxanthin Enhances the Antifibrotic Potential of Placenta-derived Mesenchymal Stem Cells in a CCl4-induced Mouse Model of Liver Fibrosis

Curr Stem Cell Res Ther. 2024 Jan 8. doi: 10.2174/011574888X279940231206100902. Online ahead of print.

Authors

Vasilii Slautin¹, Konstantin Konyshev^{1

2}, Ilya Gavrilov^{1

2}, Olga Beresneva¹, Irina Maklakova^{1

2}, Dmitry Grebnev^{1

2}

Affiliations

¹ Department of Pathophysiology , Ural State Medical University, 3, Repin Street, 620028, Yekaterinburg, Russia.
² Institute of Medical Cell Technologies, 22a, Karl Marx Street, 620026, Yekaterinburg, Russia.

PMID: 38204245
DOI: 10.2174/011574888X279940231206100902

Abstract

Background: The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis.

Aim: This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis.

Methods: After PD-MSCs isolation and identification, outbred ICR/CD1 mice were divided into five groups: Control group, CCl4 group (CCl4), Fx group (CCl4+Fx), PD-MSCs group (CCl4+MSCs) and cotreatment group (CCl4+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+), matrix metalloproteinases (MMP-9+, MMP-13+), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas, and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β), hepatic growth factor (HGF), procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay.

Results: Compared to the single treatment with PD-MSCs or Fx, their combined administration significantly reduced liver enzyme activity, the severity of liver fibrosis, the proinflammatory cytokine levels, TGF-β level, α-SMA+, TIMP-1+ areas and the number of positive cells in them, and increased HGF level, MMP-13+, and MMP-9+ areas.

Conclusion: Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis, but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.

Keywords: Liver fibrosis; MSCs-based therapy; TGF-β.; fucoxanthin; hepatic stellate cells; placenta-derived mesenchymal stem cells.