Pharmacological Inhibition of Gal‐3 in Mesenchymal Stem Cells Enhances Their Capacity to Promote Alternative Activation of Macrophages in Dextran Sulphate Sodium‐Induced Colitis

Marković, Bojana Simović; Nikolić, Aleksandar; Gazdic, Marina; Nurković, Jasmin; Djordjevic, Irena; Arsenijević, Nebojša; Stojković, Miodrag; Lukic, Miodrag L.; Volarević, Vladislav

doi:10.1155/2016/2640746

Cited by 32 publications

(16 citation statements)

References 39 publications

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“…Recently, by using murine model of acute colitis induced by dextran sodium sulfate (DSS), we showed that pharmacological inhibition of Gal‐3 in BM‐MSCs enhances their capacity to promote alternative activation of peritoneal macrophages in vitro and in vivo . Injection of BM‐MSCs cultured in the presence of Gal‐3 inhibitor increased concentration of IL‐10 in sera of DSS‐treated animals and markedly enhanced presence of alternatively activated and IL‐10 producing macrophages in the colons of DSS‐treated mice leading to the attenuation of colitis . In accordance with these findings, results obtained in a large number of clinical trials indicate therapeutic potential of MSCs in the treatment of inflammatory bowel diseases (IBDs).…”

Section: Introductionsupporting

confidence: 58%

“…MSCs produce Galectin‐3 (Gal‐3), a protein known to affect proliferation, adhesion, and migration of immune cells . Recently, by using murine model of acute colitis induced by dextran sodium sulfate (DSS), we showed that pharmacological inhibition of Gal‐3 in BM‐MSCs enhances their capacity to promote alternative activation of peritoneal macrophages in vitro and in vivo . Injection of BM‐MSCs cultured in the presence of Gal‐3 inhibitor increased concentration of IL‐10 in sera of DSS‐treated animals and markedly enhanced presence of alternatively activated and IL‐10 producing macrophages in the colons of DSS‐treated mice leading to the attenuation of colitis .…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

et al. 2017

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Stem cell-based therapy is considered to be a new hope in transplantation medicine. Among stem cells, mesenchymal stem cells (MSCs) are, due to their differentiation and immuno-modulatory characteristics, the most commonly used as therapeutic agents in the treatment of immune-mediated diseases. MSCs migrate to the site of inflammation and modulate immune response. The capacity of MSC to alter phenotype and function of immune cells are largely due to the production of soluble factors which expression varies depending on the pathologic condition to which MSCs are exposed. Under inflammatory conditions, MSCs-derived factors suppress both innate and adaptive immunity by attenuating maturation and capacity for antigen presentation of dendritic cells, by inducing polarization of macrophages towards alternative phenotype, by inhibiting activation and proliferation of T and B lymphocytes and by reducing cytotoxicity of NK and NKT cells. In this review, we emphasized current findings regarding immuno-modulatory effects of MSC-derived factors and emphasize their potential in the therapy of immune-mediated diseases. © 2017 BioFactors, 43(5):633-644, 2017.

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Section: Introductionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

et al. 2017

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“…Simovic et al found that Gal‐3 can promote the activation of the NOD‐like receptor family, the pyrin domain containing 3 (NLRP3) inflammasome, and the production of IL‐1β in macrophages . Inhibition of Gal‐3 activation pushes macrophages toward M2 polarization via upregulating the expression of IL‐10 in vitro and in vivo, suggesting that AGEs/Gal‐3 play roles in macrophage polarization that modulate the responsiveness of innate and adaptive immunity.…”

Section: Micro‐environmental and Intracellular Metabolism On Atm Polamentioning

confidence: 99%

Micro‐environment and intracellular metabolism modulation of adipose tissue macrophage polarization in relation to chronic inflammatory diseases

Zhu

Chen

et al. 2018

Diabetes Metabolism Res

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The accumulation and pro-inflammatory polarization of immune cells, mainly macrophages, in adipose tissue (AT) are considered crucial factors for obesity-induced chronic inflammatory diseases. In this review, we highlighted the role of adipose tissue macrophage (ATM) polarization on AT function in the obese state and the effect of the micro-environment and intracellular metabolism on the dynamic switch of ATMs into their pro-inflammatory or anti-inflammatory phenotypes, which may have distinct influences on obesity-related chronic inflammatory diseases. Obesity-associated metabolic dysfunctions, including those of glucose, fatty acid, cholesterol, and other nutrient substrates such as vitamin D and iron in AT, promote the pro-inflammatory polarization of ATMs and AT inflammation via regulating the interaction between ATMs and adipocytes and intracellular metabolic pathways, including glycolysis, fatty acid oxidation, and reverse cholesterol transportation. Focusing on the regulation of ATM metabolism will provide a novel target for the treatment of obesity-related chronic inflammatory diseases, including insulin resistance, cardiovascular diseases, and cancers.

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“…In the peritoneal cavity of mice with acute colitis, the amount of CD206+ M2 macrophages was significantly increased by MSCs with IL-1 pretreatment, which inhibited the number of CD11c+ M1 macrophages, thus alleviating inflammatory responses in the intestinal mucosa [ 84 ]. Semitic et al also demonstrated that MSCs mediated the alternative activation of macrophages through the inhibition of galectin-3 [ 85 ]. We have demonstrated that hucMSCs could repair DSS-induced IBD through the regulation of 15-LOX-1 expression and the modulation of inflammatory responses in macrophages [ 86 ].…”

Section: Mesenchymal Stem Cells Regulate Macrophages To Treat Inflammmentioning

confidence: 99%

Crosstalk between mesenchymal stem cells and macrophages in inflammatory bowel disease and associated colorectal cancer

Mao¹,

Kang²,

Cai³

et al. 2017

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Mesenchymal stem cells (MSCs) are attractive seed cells for immunotherapy, tissue engineering and regenerative medicine due to their self-renewal and multidirectional differentiation abilities, diverse immunoregulatory functions and ease of isolation from a wide range of tissues. MSCs exert their immunoregulatory effect on immune cells via cell-to-cell contact and paracrine mechanisms. In turn, MSCs can also be modulated by immune cells. Macrophages are constantly present in the mucosa of the intestinal tract of mammals and play an important role in the development and progression of inflammatory bowel disease (IBD), a chronic and recurrent inflammatory disease of the gastrointestinal tract characterized by idiopathic mucosal inflammation. The increased morbidity and mortality of IBD have made it a disease hard to cure in the clinic. MSCs have emerged as an important tool for IBD therapy due to their abilities to differentiate into enterocyte-like cells and regulate inflammatory cells, especially macrophages. In this review, we discuss the recent advances in the interaction between MSCs and macrophages in diseases, with an emphasis on IBD. We propose that an optimized MSC-based therapy would provide a novel strategy for the treatment of IBD and the prevention of IBD-associated colorectal cancer (CRC).

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Pharmacological Inhibition of Gal‐3 in Mesenchymal Stem Cells Enhances Their Capacity to Promote Alternative Activation of Macrophages in Dextran Sulphate Sodium‐Induced Colitis

Cited by 32 publications

References 39 publications

Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

Micro‐environment and intracellular metabolism modulation of adipose tissue macrophage polarization in relation to chronic inflammatory diseases

Crosstalk between mesenchymal stem cells and macrophages in inflammatory bowel disease and associated colorectal cancer

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