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.

Background Alveolar echinococcosis (AE) is a zoonotic disease caused by the larval stage of Echinococcus multilocularis parasitizing in the human liver, causing local pathological changes in the liver and manifesting as hyperplasia, liver fibrosis, atrophy, degeneration, and necrosis. Here, we report a method that can simultaneously isolate hepatocytes and hepatic stellate cells (HSCs) from mice infected with Echinococcus multilocularis. Methods A mouse model of AE was established. Hepatocytes and HSCs were isolated from mouse liver using a two‐step method combining in situ collagenase perfusion and gradient centrifugation. Expressions of Alb, Desmin, and α‐SMA were detected with immunofluorescence to identify the isolated hepatocytes and HSCs. Results The viability and purity of hepatocytes and HSCs both reached 90% or above. For hepatocytes, clear cell boundaries were observed, and the nuclei were round or oval, with clear nucleoli. There was a homogeneous distribution of the hepatocyte marker Alb in the cytoplasm of hepatocytes. Lipid droplets and Desmin expression were observed in the cytoplasm of freshly isolated HSCs. During the activation of HSCs, the lipid droplets gradually decreased and disappeared with a high expression of α‐SMA. Conclusion Hepatocytes and HSCs are simultaneously isolated. This may provide a research tool to investigate the interaction between hepatocytes and HSCs and to investigate the mechanism of Echinococcus multilocularis infection‐induced liver pathological changes.

Abstract ObjectiveAlveolar echinococcosis (AE) is a chronic disease caused by the larval stage of Echinococcus multilocularis. Assessing the metabolic activity of AE lesions is critical to evaluate disease progression and survey treatment options. There is an urgent need to identify more rapid, convenient, and non-invasive clinical detection methods to substitute the current techniques. Herein, we evaluated the viability of platelet-derived growth factor-B B (PDGF-BB) as a biomarker for detecting the metabolic activity of AE patients. Concentration of serum PDGF-BB homodimers (sPDGF-BB) was assessed via ELISA. Correlations of PDGF-BB expression levels with clinicopathological features of AE patients were analyzed using SPSS. ResultsThe concentrations of sPDGF-BB were significantly lower in AE patients (p<0.0001), particularly in HMAE patients (p<0.05). The expression levels of PDGF-BB were significantly higher in CLT in AE patients (p<0.0001). We found that metabolically active AE and sPDGF-BB are significantly negatively correlated (r=-0.624, p=0.0004). Besides, the local expression levels of PGFD-BB was positively correlated with metabolic activity, the PNM stage, and lesion size. Notably, the sPDGF-BB levels were proposed as a potential biomarker for assessing metabolic activity of AE, with 85.7% sensitivity and 81% specificity (95% confidence interval, P = 0.003).

ObjectiveAlveolar echinococcosis (AE) is a chronic disease caused by the larval stage of Echinococcus multilocularis. Assessing the metabolic activity of AE lesions is critical to evaluate disease progression and survey treatment options. There is an urgent need to identify more rapid, convenient, and noninvasive clinical detection methods to substitute the current techniques. Herein, we evaluated the viability of platelet-derived growth factor-B B (PDGF-BB) as a biomarker for detecting the metabolic activity of AE patients. Concentration of serum PDGF-BB homodimers (sPDGF-BB) was assessed via ELISA. Correlations of PDGF-BB expression levels with clinicopathological features of AE patients were analyzed using SPSS. ResultsThe concentrations of sPDGF-BB were signi cantly lower in AE patients (p<0.0001), particularly in HMAE patients (p<0.05). The expression levels of PDGF-BB were signi cantly higher in CLT in AE patients (p<0.0001). We found that metabolically active AE and sPDGF-BB are signi cantly negatively correlated (r=-0.624, p=0.0004). Besides, the local expression levels of PGFD-BB was positively correlated with metabolic activity, the PNM stage, and lesion size. Notably, the sPDGF-BB levels were proposed as a potential biomarker for assessing metabolic activity of AE, with 85.7% sensitivity and 81% speci city (95% con dence interval, P = 0.003).

Objective Alveolar echinococcosis (AE) is a chronic disease caused by the larval stage of Echinococcus multilocularis. Assessing the metabolic activity of AE lesions is critical to evaluate disease progression and survey treatment options. There is an urgent need to identify more rapid, convenient, and non-invasive clinical detection methods to substitute the current techniques. Herein, we evaluated the viability of platelet-derived growth factor-B B (PDGF-BB) as a biomarker for detecting the metabolic activity of AE patients. Concentration of serum PDGF-BB homodimers (sPDGF-BB) was assessed via ELISA. Correlations of PDGF-BB expression levels with clinicopathological features of AE patients were analyzed using SPSS. Results The concentrations of sPDGF-BB were significantly lower in AE patients (p<0.0001), particularly in High Metabolically Active AE patients (HMAE) patients (p<0.05). The expression levels of PDGF-BB were significantly higher in close liver tissue (CLT) in AE patients (p<0.0001). We found that metabolically active AE and sPDGF-BB are significantly negatively correlated (r=-0.624, p=0.0004). Besides, the local expression levels of PDGF-BB was positively correlated with metabolic activity, PNM stage, and lesion size. Notably, the sPDGF-BB levels were proposed as a potential biomarker for assessing metabolic activity of AE, with 81% sensitivity and 85.7% specificity (95% confidence interval, p = 0.003).