Activation of hepatic stellate cells after phagocytosis of lymphocytes: A novel pathway of fibrogenesis

Muhanna, Nidal; Doron, S.; Wald, Ori; Horani, Amjad; Eid, Ahmed; Pappo, Orit; Friedman, Scott L.; Safadi, Rifaat

doi:10.1002/hep.22413

Cited by 128 publications

(131 citation statements)

References 75 publications

(90 reference statements)

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“…238 Moreover, MSCs are able to modulate HeSC immune function and to induce HeSC apoptosis, which likely also contribute to their anti-fibrotic effects. 187,239 In di Bonzo et al, 50 although a significant proportion of MSCs were found to generate myofibroblasts, similar amounts of unidentified cells with low nuclear/cytoplasmic ratio were also reported, suggesting that they are likely refractable to myofibroblast differentiation under a pro-fibrogenic microenvironment. The latter population might be responsible for the beneficial effects usually retrieved when applying MSCs.…”

Section: Mscs and Their Anti-fibrotic Potentialmentioning

confidence: 95%

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

et al. 2010

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Mesenchymal stem (stromal) cells (MSCs) are a source of circulating progenitors that are able to generate cells of all mesenchymal lineages and to cover cellular demands of injured tissues. The extent of their transdifferentiation plasticity remains controversial. Cells with MSC properties have been obtained from diverse tissues after purification and expansion in vitro. These cellular populations are heterogeneous and under certain conditions show pluripotent-like properties. MSCs present immunosuppressive and anti-inflammatory features and high migratory capacity toward inflamed or remodeling tissues. In this study we review available data regarding factors and signaling axes involved in the chemoattraction and engraftment of MSCs to an injured tissue or to a tissue undergoing active remodeling. Moreover, experimental evidence in support of uses of MSCs as vehicles of therapeutic genes is discussed. Because of its regenerative capacity and its particular immune properties, the liver is a good model to analyze the potential of MSCbased therapies. Finally, the potential application of MSCs and genetically modified MSCs in liver fibrosis and hepatocellular carcinoma (HCC) is proposed in view of available evidence.

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Section: Mscs and Their Anti-fibrotic Potentialmentioning

confidence: 95%

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

et al. 2010

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“…Additionally, HSC activation by melanoma-derived soluble factors results in the recruitment of LSECs, promoting the development of new vessels (97). On the other hand, activated HSCs have the ability to phagocytose lymphocytes during liver inflammation (98), to abrogate CD8 + T cell-mediated immunity (99), and to enhance the recruitment of immunosuppressive cells (100), thus impeding the appropriate anti-tumor function in an ICAM-1-dependent pathway, and facilitating tumor expansion.…”

Section: Tumor Cell Extravasation: Opening the Liver's Doors To Invadmentioning

confidence: 99%

Role of liver ICAM-1 in metastasis

2017

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Abstract. Intercellular adhesion molecule (ICAM)-1, is a transmembrane glycoprotein of the immunoglobulin (Ig)-like superfamily, consisting of five extracellular Ig-like domains, a transmembrane domain and a short cytoplasmic tail. ICAM-1 is expressed in various cell types, including endothelial cells and leukocytes, and is involved in several physiological processes. Furthermore, it has additionally been reported to be expressed in various cancer cells, including melanoma, colorectal cancer and lymphoma. The majority of studies to date have focused on the expression of the ICAM-1 on the surface of tumor cells, without research into ICAM-1 expression at sites of metastasis. Cancer cells frequently metastasize to the liver, due to its unique physiology and specialized liver sinusoid capillary network. Liver sinusoidal endothelial cells constitutively express ICAM-1, which is upregulated under inflammatory conditions. Furthermore, liver ICAM-1 may be important during the development of liver metastasis. Therefore, it is necessary to improve the understanding of the mechanisms mediated by this adhesion molecule in order to develop host-directed anticancer therapies.

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“…TumoriTreg seem cells by activated hepatic stellate cells [31] , and the up regulation of inhibitory or downregulation of activating receptors, respectively [32] .…”

Section: Regulatory T Lymphocytesmentioning

confidence: 99%

Immunology of hepatocellular carcinoma

Sachdeva

Chawla

Arora

2015

WJH

100

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Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system (including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells (e.g. , dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC.

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Activation of hepatic stellate cells after phagocytosis of lymphocytes: A novel pathway of fibrogenesis

Cited by 128 publications

References 75 publications

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

Role of liver ICAM-1 in metastasis

Immunology of hepatocellular carcinoma

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