Abstract
BackgroundAlveolar 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 findingsC57BL/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.ConclusionsADSCs 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.
Highlights
Alveolar echinococcosis (AE), one of the most dangerous zoonoses in both developing and developed Northern Hemisphere countries, is caused by infection with larval stages of the tapeworm Echinococcus multilocularis (E. multilocularis) [1,2]
In view of the therapeutic potential of adipose-derived stem cells (ADSCs), we investigated whether Adipose-derived stem cells (ADSCs) transplantation has the ability to control or reverse fibrosis progression in the liver of Echinococcus multilocularis (E. multilocularis) infected mice
One day after establishing E. multilocularis infection mice models, CM-DiI labeled ADSCs were transplanted into the mice via tail vein injection
Summary
Alveolar echinococcosis (AE), one of the most dangerous zoonoses in both developing and developed Northern Hemisphere countries, is caused by infection with larval stages (metacestode) of the tapeworm Echinococcus multilocularis (E. multilocularis) [1,2]. The continuous growth of metacestodes in liver tissues of their intermediate hosts obstructs blood vessels and bile ducts, leading to organ failure [4]. The development of severe fibrosis surrounding the lesion is a feature of AE, and excess fibrosis can damage the liver parenchyma. We previously found that the fibrotic "barrier" at the periphery of the lesion constantly erodes the surrounding liver parenchyma, leading to death of the host [6]. Hepatectomy is the sole curative treatment option for AE, it is not suitable for patients with severe disease in whom the lesions surpass the resectability threshold or those with decompensated liver dysfunction caused by AE. In terms of pharmaceutical treatment, the fibrotic "barrier" around the lesion limits the efficacy of benzimidazole-based chemotherapeutic drugs [7]. There is an urgent need to develop new therapeutic approaches for E. multilocularis-induced liver fibrosis, thereby minimizing liver damage and allowing antiparasitic drugs to effectively penetrate the lesion
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