Human Gingiva-Derived Mesenchymal Stem Cells Modulate Monocytes/Macrophages and Alleviate Atherosclerosis

Zhang, Ximei; Huang, Feng; Li, Weixuan; Dang, Jun; Jia, Yuan; Wang, Julie; Zeng, Dong Lan; Sun, Can Xing; Liu, Yan Ying; Ao, Qian; Tan, Hongmei; Su, Wenru; Qian, Xiaoxian; Olsen, Nancy J.; Zheng, Song Guo

doi:10.3389/fimmu.2018.00878

Cited by 82 publications

(87 citation statements)

References 87 publications

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“…The significant therapeutic effects observed in treating graft vs host disease (GVHD) and rheumatoid arthritis via a mechanism related to that of Tregs increased our interest in GMSCs. GMSCs have been shown to suppress the differentiation, frequency, activation and cytokine production of inflammatory monocytes and macrophages . Here, we demonstrated that GMSC treatment represents a promising strategy to prevent the development of IBD compared to fibroblasts.…”

Section: Discussionmentioning

confidence: 78%

Human gingiva‐derived mesenchymal stem cells alleviate inflammatory bowel disease via IL‐10 signalling‐dependent modulation of immune cells

Zhang

et al. 2019

Scand J Immunol

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Current evidence indicates that inflammatory bowel disease (IBD) is caused primarily by impaired mucosal immunity, resulting in an imbalance between epithelial barrier function and tissue inflammation. Human gingiva‐derived mesenchymal stem cells (GMSCs) exhibit immunomodulatory and anti‐inflammatory effects in a variety of immunity‐ and inflammation‐associated diseases. However, the role of GMSCs in treating IBD has not been elucidated. Our study, therefore, examined the therapeutic effect and mechanism of GMSCs in a murine colitis model of IBD. Our results indicate that the infusion of GMSCs significantly prolonged survival and relieved symptoms. Phenotype analyses showed that the frequencies of NK1.1+ and CD11b+ cells, as well as CD4 T cells in the spleen, were suppressed in GMSC‐treated mice compared with the PBS‐ or fibroblast‐treated control groups. Additionally, GMSC treatment markedly increased the numbers of interleukin (IL)‐10+ regulatory T cells, reduced the secretion of pro‐inflammatory cytokines, and increased production of anti‐inflammatory cytokines. A mechanistic study revealed that anti‐IL‐10R antibody abolished the protective effect of GMSCs compared with mice treated with anti‐IgG antibody. Thus, our results indicate that GMSCs play a critical role in alleviating colitis by modulating inflammatory immune cells via IL‐10 signalling.

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Section: Discussionmentioning

confidence: 78%

Human gingiva‐derived mesenchymal stem cells alleviate inflammatory bowel disease via IL‐10 signalling‐dependent modulation of immune cells

Zhang

et al. 2019

Scand J Immunol

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“…Human gingival derived MSCs (GMSCs) are another member of MSCs and have been considered as a promising source of MSCs for their ease and safe isolation and fast proliferation properties [49]. In line with other studies, our group recently observed that infusion of GMSCs can also alleviate atherosclerosis in ApoE −/− Mice [17]. In this study, atherosclerotic models were built by feeding 8 week old male ApoE −/− mice a high fat diet for 12 weeks, and GMSCs (2X10 6 ) were administrated every three weeks from the first day of high fat diet for a total of three times.…”

Section: Human Gingival-derived Mscs In Atherosclerosismentioning

confidence: 54%

“…Due to their multiple differentiation capabilities, inflammatory and immune modulation function, MSCs have been explored as an attractive therapeutic agent in various diseases including allergic conjunctivitis, acute lung injury, myocardial infarction, allergic rhinitis, Alzheimer's disease, and type 1 diabetes [9][10][11][12][13][14][15]. In light of the critical role inflammatory processes have in the initiation and progression of atherosclerosis, our group and others have transfered MSCs to atherosclerotic animal models revealing MSCs were able to alleviate atherosclerosis [16][17][18]. These results are important for further investigation into its potential clinical application.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells: A Potential Promise in Treating Atherosclerosis?

Zhang¹,

Wang²,

Colello³

et al. 2018

Preprint

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Atherosclerosis is a chronic inflammatory disease which results in thickening of the vessel wall and narrowing of the lumen. It is a leading cause of death worldwide. Preventive treatment is taken into prioritized consideration since currently no effective approaches to cure atherosclerosis are available. These treatments mainly focus on lowering blood cholesterol levels, especially LDL-C, by statins. Even so, lowering lipid levels is not sufficient to reduce the risk of cardiovascular events in all patients. Recently, atherosclerosis has increasingly been recognized as a chronic inflammatory disease involving the immune system, initiating new therapeutic approaches which could alleviate or prevent atherosclerosis by modulating inflammation. Mesenchymal stem cells (MSCs) have emerged as a promising option to relieve inflammation and balance immune responses in inflammatory diseases. Several studies including our group also reported that MSCs may be a new therapeutic option for atherosclerosis. This review summarizes the updated state of our knowledge in the administration of MSCs to alleviate atherosclerosis and discusses some of the key unresolved challenges that need to be solved in future studies.

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“…Compared with the control group where atherosclerotic mice models were fed with western diet, atherosclerotic plaque size and lipid deposition were significantly reduced in mice after BMSC transplantation. Moreover, the number of activated macrophages with inflammatory phenotype and macrophage-derived foam cells was all reduced [61].…”

Section: Bmscs Affect Macrophages Polarizationmentioning

confidence: 98%

The involving progress of MSCs based therapy in atherosclerosis

2020

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Atherosclerosis is a chronic progressive vascular inflammation characterized by lipid deposition and plaque formation, for which vascular cell dysfunction and impaired immune responses are involved. Up to now, lipidlowering drugs remain the main therapy for treating atherosclerosis; however, the surgical or interventional therapy is often applied, and yet, morbidity and mortality of such cardiovascular disease remain high worldwide. Over the past decades, an anti-inflammatory approach has become an important therapeutic target for dealing with atherosclerosis, as altered immune responses have been regarded as an essential player in the pathological process of vascular abnormality induced by hyperlipidemia. Interestingly, mesenchymal stem cells, one type of stem cells with the capabilities of self-renewal and multi-potential, have demonstrated their unique immunomodulatory function in the various pathological process, especially in atherosclerosis. While some controversies remain regarding their therapeutic efficacy and working mechanisms, our present review aims to summarize the current research progress on stem cell-based therapy, focusing on its immunomodulatory effects on the pathogenesis of atherosclerosis and how endothelial cells, smooth muscle cells, and other immune cells are regulated by MSCbased therapy.

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Human Gingiva-Derived Mesenchymal Stem Cells Modulate Monocytes/Macrophages and Alleviate Atherosclerosis

Cited by 82 publications

References 87 publications

Human gingiva‐derived mesenchymal stem cells alleviate inflammatory bowel disease via IL‐10 signalling‐dependent modulation of immune cells

Human gingiva‐derived mesenchymal stem cells alleviate inflammatory bowel disease via IL‐10 signalling‐dependent modulation of immune cells

Mesenchymal Stem Cells: A Potential Promise in Treating Atherosclerosis?

The involving progress of MSCs based therapy in atherosclerosis

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