PLoS neglected tropical diseases · 2022
Transplantation of adipose-derived stem cells ameliorates Echinococcus multilocularis-induced liver fibrosis in mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Yang Ning, Ma Wenmei, Ke Ying, Liu Hui, Chu Jin, Sun Li, Lü Guodong, Bi Xiaojuan, Lin Renyong
Аннотация
BACKGROUND: Alveolar echinococcosis (AE) can cause severe liver fibrosis and could be fatal if left untreated. Currently, there are no effective therapeutic options for AE-induced liver fibrosis. In view of the therapeutic potential of adipose-derived stem cells (ADSCs), we investigated whether ADSCs transplantation has the ability to control or reverse fibrosis progression in the liver of Echinococcus multilocularis (E. multilocularis) infected mice.
METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice infected with E. multilocularis through portal vein inoculation were intravenously injected with ADSCs isolated from inguinal adipose tissues of 6-8 weeks old mice. Histopathological analysis including heamatoxylin & eosin staining as well as Masson's trichrome staining, and Sirius red staining were performed to access the degree of liver fibrosis. Histopathological examination 30 days after ADSCs transplantation revealed that ADSCs significantly decreased the degree of liver fibrosis in E. multilocularis infected mice by inhibiting the expressions of α-SMA and type 1 collagen deposition. In addition, compared to the non-transplanted group, ADSCs transplantation reduced fibrotic areas in E. multilocularis infected mice. We also found that ADSCs transplantation significantly down-regulated TGF-β1 and TGF-βR expressions, while up-regulating Smad7 expression in the TGF-β/Smad signaling pathway.
CONCLUSIONS: ADSCs can alleviate Echinococcus multilocularis infection-induced liver fibrosis by modulating the activity level of the TGF-β/Smad7 signaling pathway and provide a potential therapeutic approach for E. multilocularis-induced fibrosis.
METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice infected with E. multilocularis through portal vein inoculation were intravenously injected with ADSCs isolated from inguinal adipose tissues of 6-8 weeks old mice. Histopathological analysis including heamatoxylin & eosin staining as well as Masson's trichrome staining, and Sirius red staining were performed to access the degree of liver fibrosis. Histopathological examination 30 days after ADSCs transplantation revealed that ADSCs significantly decreased the degree of liver fibrosis in E. multilocularis infected mice by inhibiting the expressions of α-SMA and type 1 collagen deposition. In addition, compared to the non-transplanted group, ADSCs transplantation reduced fibrotic areas in E. multilocularis infected mice. We also found that ADSCs transplantation significantly down-regulated TGF-β1 and TGF-βR expressions, while up-regulating Smad7 expression in the TGF-β/Smad signaling pathway.
CONCLUSIONS: ADSCs can alleviate Echinococcus multilocularis infection-induced liver fibrosis by modulating the activity level of the TGF-β/Smad7 signaling pathway and provide a potential therapeutic approach for E. multilocularis-induced fibrosis.