Immunomodulatory role of mesenchymal stem cell therapy in liver fibrosis

Liu, Peng; Qian, Ye-Rong; Liu, Xin; Zhu, Xiaohong; Zhang, Xufeng; Lv, Yi; Xiang, Jun

doi:10.3389/fimmu.2022.1096402

Cited by 17 publications

(6 citation statements)

References 98 publications

(120 reference statements)

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“…Under the continuous stimulation of chronic in ammation, various cytokines and brous mediators associated with injury are released, activating the quiescent HSCs into proliferative, contractile, and brotic liver myo broblasts, further leading to abnormal deposition of extracellular matrix and formation of liver brosis 17 . Pro-in ammatory mediators, oxidative stress molecules, and in ammatory stimulants produced by apoptosis and necrosis of liver injured cells initiate the activation of HSCs 18,19 . And TGF-β is considered to be one of the most crucial signaling molecules for the activation of HSCs 20 .…”

Section: Discussionmentioning

confidence: 99%

The therapeutic effect and mechanism of CXCL9-overexpressed umbilical cord mesenchymal stem cells on liver fibrosis

Li,

Zhang,

Liu

et al. 2024

Preprint

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Umbilical cord mesenchymal stem cells (UC-MSC) transplantation has become a promising treatment for liver fibrosis. However, UC-MSC have limited anti-fibrosis ability for various reasons. In this study, we aimed to determine if the overexpression of CXCL9 in UC-MSC (CXCL9-UC-MSCs) could have synergistic anti-fibrosis effects and explore the possible mechanism. We analyzed the expression of α-SMA and Collagen-III in rats and LX-2 cells, as well as the inhibition of the TGF-β1/Smad3 pathway, approched by staining HE staining, immunohistochemistry staining, and western-blot. After the cell therapy, pathological staining and liver function indicated that the area of liver fibrosis in the rats were reduced, the hepatocellular necrosis and liver function damage were improved, and the improvement was more significant in the CXCL9-UC-MSC intervention group. Furthermore, the expression levels of α-SMA, Collagen-III, TGF-β1 and pSmad3 in the liver and LX-2 cells were decreased more obviously atfer the CXCL9 intervention. Meanwhile, the abilities of proliferation, viability and invasiveness of LX-2 cells were also significantly inhibited with the intervention of CXCL9. In conclusion, CXCL9 overexpression of UC-MSC inhibited the activation of TGF-β1/Smad3 signaling pathway, and reduced the expressions of α-SMA and Collagen-III in liver and LX-2 cells, thus playing a more significant anti-fibrosis effect.

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Section: Discussionmentioning

confidence: 99%

The therapeutic effect and mechanism of CXCL9-overexpressed umbilical cord mesenchymal stem cells on liver fibrosis

Li,

Zhang,

Liu

et al. 2024

Preprint

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“…191 Different types of T cell subsets, including Th1, Th17, Th22, and Treg cells, along with the cytokines they produce, have been implicated in the progression of intestinal fibrosis, among them, MSCs and their EVs can reduce fibrosis by modulating the immune system. 190,192 In addition, MSCs and their derived EVs secrete hepatocyte growth factor and TGF-β to reduce fibrosis, and also inhibit dermal fibroblast-myofibroblast transformation by inhibiting the TGF-β1/Smad2/3 signaling pathway. 193,194 Antibiotics can target bacterial infections in the gut, reduce inflammation, and may help improve symptoms.…”

Section: Anti-fibrosis Anti-bacteria and Angiogenesismentioning

confidence: 99%

Mesenchymal Stromal Cells: New Generation Treatment of Inflammatory Bowel Disease

Wei,

Li,

Wang

et al. 2024

JIR

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Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.

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“…Alcohol metabolism, especially through CYP2E1, leads to the release of ROS and generation of lipid peroxidation products. ROS are also generated from mitochondria during alcohol metabolism (Liu et al, 2023).…”

Section: Paracrine Effect Of Hepatocytesmentioning

confidence: 99%

Alcohol-induced hepatic fibrosis and the relation between Hepcidin and liver fibrosis

Ali,

Aborehab,

Saleh

et al. 2024

Records of Pharmaceutical and Biomedical Sciences

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Alcoholic liver disease (ALD) is a worldwide health problem that may lead to development of fatty liver steatosis, hepatitis and cirrhosis. Alcohol is known to exert a harmful effect on a variety of human tissues. In particular, the liver is the major site of alcohol-induced damage because it is the direct recipient of the blood that contains elevated levels of alcohol, and it is the major organ responsible for alcohol metabolism. The damage caused by ethanol is mainly attributed to its metabolic process that results in production of acetaldehyde and reactive oxygen species (ROS) such as hydrogen peroxide, superoxide and free hydroxyl radical. These metabolites cause depletion of reduced glutathione (GSH), peroxidation of cellular membranes, oxidation of macro-molecules such as proteins and nucleic acids, and eventually lead to progressive injury of hepatocytes. Additionally, ethanol and its metabolic products enhance the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The enhanced production of those inflammation factors; stimulated partially by oxidative stress; results in cytokine imbalance and immune disorders, leading to further hepatic damage. Thus, agents with anti-inflammatory and anti-oxidative properties might be potential candidates for protection against alcohol-induced liver disease. The metabolic functions of the alcoholic liver are seriously affected. Disorders in iron metabolism are characteristic of ALD. Abnormal levels of iron, ferritin, and transferrin were reported in ALD. Hepcidin, the principle hepatic regulator of the metabolism of iron, is decreased in ALD.

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Immunomodulatory role of mesenchymal stem cell therapy in liver fibrosis

Cited by 17 publications

References 98 publications

The therapeutic effect and mechanism of CXCL9-overexpressed umbilical cord mesenchymal stem cells on liver fibrosis

The therapeutic effect and mechanism of CXCL9-overexpressed umbilical cord mesenchymal stem cells on liver fibrosis

Mesenchymal Stromal Cells: New Generation Treatment of Inflammatory Bowel Disease

Alcohol-induced hepatic fibrosis and the relation between Hepcidin and liver fibrosis

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