Co‐cultured bone marrow mesenchymal stem cells repair thioacetamide‐induced hepatocyte damage

Chen, Hung-Chiuan; Awale, Suresh; Wu, Chean-Ping; Lee, Hu-Hui; Wu, Hsi-Tien

doi:10.1002/cbin.11453

Cited by 6 publications

(4 citation statements)

References 61 publications

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“…Figure also shows that the iron content of rats in group 2 was significantly lower than that of rats in group 1 on days 42 and 56, which may be due to the repair effect of BMSCs on hepatocyte damage. This finding was consistent with the antifibrosis effect of BMSCs recorded in the literature . However, the mechanism of BMSCs inhibiting liver fibrosis is beyond the aim of the current study and will be discussed in our future work.…”

Section: Resultssupporting

confidence: 92%

“…This finding was consistent with the antifibrosis effect of BMSCs recorded in the literature. 30 However, the mechanism of BMSCs inhibiting liver fibrosis is beyond the aim of the current study and will be discussed in our future work. The distribution of HID of rats in group 1 was measured on days 0, 7, 14, 21, 28, 42, and 56, as shown in Figure 3.…”

Section: ■ Introductionmentioning

confidence: 96%

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Determination of Hepatic Iron Deposition in Drug-Induced Liver Fibrosis in Rats by Confocal Micro-XRF Spectrometry

Xia

Zhou

et al. 2022

ACS Omega

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Liver fibrosis is the intermediate process and inevitable stage of the development of chronic liver disease into cirrhosis. Reducing the degree of liver fibrosis plays an extremely important role in treating chronic liver disease and preventing liver cirrhosis and liver cancer. The formation of liver fibrosis is affected by iron deposition to a certain extent, and excessive iron deposition further induces liver cirrhosis and liver cancer. Herein, confocal microbeam X-ray fluorescence (μ-XRF) was used to determine the intensity and biodistribution of iron deposition at different time points in the process of liver fibrosis induced by thioacetamide (TAA) in rats. To our best knowledge, this is the first study using confocal μ-XRF to analyze hepatic iron deposition in hepatic fibrosis. The results showed that there are minor and trace elements such as iron, potassium, and zinc in the liver of rats. Continuous injection of TAA solution resulted in increasing liver iron deposition over time. The intensity of iron deposition in liver tissue was also significantly reduced after bone mesenchymal stem cells (BMSCs) were injected. These findings indicated that confocal μ-XRF can be used as a nondestructive and quantitative method of evaluating hepatic iron deposition in hepatic fibrosis, and iron deposition may play an important role in the progression of hepatic fibrosis induced by TAA.

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Section: Resultssupporting

confidence: 92%

Section: ■ Introductionmentioning

confidence: 96%

Determination of Hepatic Iron Deposition in Drug-Induced Liver Fibrosis in Rats by Confocal Micro-XRF Spectrometry

Xia

Zhou

et al. 2022

ACS Omega

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“…The TAA model of cirrhosis was induced as in our previous publication. 25 Male Wistar rats received ip injections with 200 mg/kg TAA (Sigma) twice a week for 12 weeks.…”

Section: Taa-induced Cirrhosis Rat Modelmentioning

confidence: 99%

Precision-Cut Liver Slices as anex vivomodel to evaluate antifibrotic therapies for liver fibrosis and cirrhosis

Wang,

Leaker,

Qiao

et al. 2023

Preprint

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BackgroundPrecision-Cut Liver Slices (PCLS) are anex vivoculture model developed to study hepatic drug metabolism. One of the main benefits of this model is that it retains the structure and cellular composition of the native liver. PCLS also represents a potential model system to study liver fibrosis in a setting that more closely approximatesin vivopathology thanin vitromethods. The aim of this study was to assess whether responses to antifibrotic interventions can be detected and quantified with PCLS.MethodsPCLS of 250 μm thickness were prepared from four different murine fibrotic liver models: choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD), thioacetamide (TAA), diethylnitrosamine (DEN), and carbon tetrachloride (CCl4). PCLS were treated with 5 μM Erlotinib for 72 hours. Histology and gene expression were then compared within vivomurine experiments and TGF-β1 activated hepatic stellate cells (HSCs). These types of PCLS characterization were also evaluated in PCLS from human cirrhotic liver.ResultsPCLS viability in culture was stable for 72 hours. Treatment of erlotinib, an EGFR inhibitor significantly inhibited the expression of profibrogenic genesIl6,Col1a1andTimp1in PCLS from CDAHFD-induced cirrhotic mice, andIl6,Col1a1andTgfb1in PCLS from TAA-induced cirrhotic rats. Erlotinib treatment of PCLS from DEN-induced cirrhotic rats inhibited the expression ofCol1a1,Timp1,Tgfb1andIl6, which was consistent with the impact of erlotinib onCol1a1andTgfb1expression inin vivoDEN-induced cirrhosis. Erlotinib treatment of PCLS from CCl4-induced cirrhosis caused reduced expression ofTimp1,Col1a1andTgfb1, which was consistent with the effect of erlotinib inin vivoCCl4-induced cirrhosis. In addition, in HSCs at PCLS from normal mice, TGF-β1 treatment upregulatedActa2(αSMA), while treatment with erlotinib inhibited the expression ofActa2. Similar expression results were observed in TGF-β1 treatedin vitroHSCs. Expression of MMPs and TIMPs, key regulators of fibrosis progression and regression, were also significantly altered under erlotinib treatment in PCLS. Expression changes under erlotinib treatment were also corroborated with PCLS from human cirrhosis samples.ConclusionThe responses to antifibrotic interventions can be detected and quantified with PCLS at the gene expression level. The antifibrotic effects of erlotinib are consistent between PCLS models of murine cirrhosis and those observedin vivoandin vitro. Similar effects were also reproduced in PCLS derived from patients with cirrhosis. PCLS is an excellent model to assess antifibrotic therapies that is aligned with the principles of Replacement, Reduction and Refinement (3Rs).

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“…These cells interact with each other through cytokines, resulting in the accumulation of extracellular matrix, as it is formed faster than it is degraded, and the gradual formation of fibrotic tissue that can further develop into cirrhosis. In particular, tumor necrosis factor α (TNFα), interleukins (ILs), and transforming growth factor β (TGF-β) are involved in the formation and development of liver fibrosis (8)(9)(10)(11). However, whether these cytokines exhibit obvious changes with the development of liver fibrosis or whether those changes differ depending on the fibrosis stimulus is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Changes in cytokines and signaling pathways in different stages of hepatic fibrosis in rats

Pi,

Hua,

Wang

et al. 2024

Preprint

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Background & Purpose: Liver fibrosis is a disease that seriously threatens people’s health, and its etiopathogenesis has not been described clearly. Experimental Approach: Female rats were subjected to common bile duct ligation (BDL) for one month, and male rats were treated with thioacetamide for 23 weeks. The expression of cytokines, signal pathways, histopathology in liver and biochemical indexes in serum were detected. Key Results: The levels of transaminases in serum and hydroxyproline and α-smooth muscle actin in the liver were remarkably increased in both models, although the degree of liver fibrosis was more severe in thioacetamide rats than in BDL rats. However, the levels of IL-1α, IL-4, IL-10, TNFα, MCP-1, PDGF-BB, p-Akt and p-STAT5 decreased, and the levels of IL-18, TGFβ1 and p-p70s6k increased in the livers of BDL rats, while the levels of IL-1α, IL-4, IL-10, IL-1β, IL-6 and IL-12p70, TNFα, MCP-1, PDGF-BB, p-CREB, p-JNK, p-NFκB, p-Akt, p-p70s6k, p-STAT3 and p-STAT5 decreased, and the levels of IL-18 and TGF-β1 increased in the livers in thioacetamide rats. Conclusion and Implications: These data suggest that TGFβ1 and IL-18 may be the main fibrogenic factors at different stages of liver fibrosis and that the levels of inflammation-associated cytokines and signaling pathway components decrease as the severity of hepatic fibrosis progresses. Therefore, it may be better to apply anti-inflammatory drugs in the early stage or use these drugs which facilitating more inflammatory cells or cytokines into liver tissue at the end stage of hepatic fibrosis.

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Co‐cultured bone marrow mesenchymal stem cells repair thioacetamide‐induced hepatocyte damage

Cited by 6 publications

References 61 publications

Determination of Hepatic Iron Deposition in Drug-Induced Liver Fibrosis in Rats by Confocal Micro-XRF Spectrometry

Determination of Hepatic Iron Deposition in Drug-Induced Liver Fibrosis in Rats by Confocal Micro-XRF Spectrometry

Precision-Cut Liver Slices as anex vivomodel to evaluate antifibrotic therapies for liver fibrosis and cirrhosis

Changes in cytokines and signaling pathways in different stages of hepatic fibrosis in rats

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