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

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

在 CCl4 诱导的肝纤维化小鼠模型中,岩藻黄素可增强胎盘间充质干细胞的抗纤维化潜能。
背景:据报道,福柯黄素(Fx)因其抗炎和抗纤维化作用而对肝脏疾病有效。基于间充质干细胞(MSCs)的疗法也被认为是一种有前景的肝纤维化治疗策略。本研究旨在确定胎盘间充质干细胞(PD-MSCs)与Fx联合治疗肝纤维化的治疗潜力,并评估其对肝纤维化发病机制主要环节的影响:方法:分离鉴定胎盘间充质干细胞(PD-MSCs)后,将杂交ICR/CD1小鼠分为5组:对照组、CCl4 组(CCl4)、Fx 组(CCl4+Fx)、PD-MSCs 组(CCl4+MSCs)和共处理组(CCl4+MSCs+Fx)。进行生化组织病理学检查。通过免疫组化染色对α-平滑肌肌动蛋白(α-SMA+)、基质金属蛋白酶(MMP-9+、MMP-13+)、基质金属蛋白酶组织抑制剂-1(TIMP-1+)区域及其阳性细胞数量进行半定量分析。肝匀浆中的转化生长因子-β(TGF-β)、肝生长因子(HGF)和胶原蛋白-1(COL1α1)以及血清中的促炎细胞因子均采用酶联免疫法测定:结果:与单一使用PD-间充质干细胞或Fx相比,两者联合使用可显著降低肝酶活性、肝纤维化严重程度、促炎细胞因子水平、TGF-β水平、α-SMA+、TIMP-1+区域及其中阳性细胞数量,并增加HGF水平、MMP-13+和MMP-9+区域:结论:Fx增强了PD-间充质干细胞对CCl4诱导的肝纤维化的治疗潜力,但要了解PD-间充质干细胞和Fx的相互影响还需要更多的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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