Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors

Liu, Siyu; Liu, Fei; Zhou, You Lang; Jin, Baeku; Sun, Qiang; Guo, Shu

doi:10.3389/fimmu.2020.01076

Cited by 59 publications

(38 citation statements)

References 158 publications

(312 reference statements)

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“…In the cocultures of mononuclear cells with MSCs, even the density of MSC monolayer may generate prosurvival signals, because the decrease of monolayer density was followed by the dosedependent increase in lymphocyte proliferation [57]. Finally, the low expression level of various surface molecules that mediate cell-to-cell contact and contribute to the immunosuppressive properties of MSCs [58] may also affect the antiproliferative activity of MSCs, which was proven in the case of CD90 [59]. Although we found that, in general, HD/ASCs and AS/ASCs exerted comparable inhibitory effects on T cell proliferation and acted mostly via soluble factors, kynurenines and PGE 2 , some dissimilarities between these cell lines were also observed.…”

Section: Stem Cells Internationalmentioning

confidence: 99%

Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients

Kuca-Warnawin

Plebańczyk

Bonek

et al. 2021

Stem Cells International

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Background. In ankylosing spondylitis (AS), accompanied by chronic inflammation, T cell expansion plays a pathogenic role; the immunoregulatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) are impaired, while functional characteristics of their adipose tissue-derived counterparts are (ASCs) unknown. Methods. We evaluated the antiproliferative activity of AS/ASCs, obtained from 20 patients, towards allogeneic and autologous T lymphocytes, using ASCs from healthy donors (HD/ASCs) as the reference cell lines. The PHA-activated peripheral blood mononuclear cells (PBMCs) were cocultured in cell-cell contact and transwell conditions with untreated or TNF + IFNγ- (TI-) licensed ASCs, then analyzed by flow cytometry to identify proliferating and nonproliferating CD4+ and CD8+ T cells. The concentrations of kynurenines, prostaglandin E2 (PGE2), and IL-10 were measured in culture supernatants. Results. In an allogeneic system, HD/ASCs and AS/ASCs similarly decreased the proliferation of CD4+ and CD8+ T cells and acted mainly via soluble factors. The concentrations of kynurenines and PGE2 inversely correlated with T cell proliferation, and selective inhibitors of these factors synthesis significantly restored T cell response. AS/ASCs exerted a similar antiproliferative impact also on autologous T cells. Conclusion. We report for the first time that despite chronic in vivo exposure to inflammatory conditions, AS/ASCs retain the normal capability to restrain expansion of allogeneic and autologous CD4+ and CD8+ T cells, act primarily via kynurenines and PGE2, and thus may have potential therapeutic value. Some distinctions between the antiproliferative effects of AS/ASCs and HD/ASCs suggest in vivo licensing of AS/ASCs.

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Section: Stem Cells Internationalmentioning

confidence: 99%

Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients

Kuca-Warnawin

Plebańczyk

Bonek

et al. 2021

Stem Cells International

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“…Previous reports have shown that the greater expression of ICAM-1 and VCAM-1 by MSC, the stronger immunosuppressive effects they exhibit (49,50). Once immune cells are attached to MSC, they activate immunosuppressive signals and undergo apoptosis, cell cycle arrest or phenotype-switch (51). In these reports, strategies based on antibody blockage targeting ICAM-1 and VCAM-1, reversed the suppression of T cell proliferation in MSC/T cell cocultures when added individually or combined.…”

Section: Discussionmentioning

confidence: 95%

Integrated Analysis of Transcriptome and Secretome From Umbilical Cord Mesenchymal Stromal Cells Reveal New Mechanisms for the Modulation of Inflammation and Immune Activation

Cruz-Barrera¹,

Flórez-Zapata

Lemus-Diaz

et al. 2020

Front. Immunol.

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Mesenchymal stromal cells (MSC) have been used in over 800 clinical trials with encouraging results in the field of transplant medicine and chronic inflammatory diseases. Today, Umbilical Cord (UC)-derived MSC are the second leading source used for clinical purposes, mainly due to its easy access and superior immune modulatory effects. Although the underlying molecular mechanisms of immune suppressive activities have not been fully understood, research over the last decade strongly suggests that MSC-mediated benefits are closely related to activation of secretome networks. Nevertheless, recent findings also point to cytokine-independent mechanisms as key players of MSC-mediated immune modulation. Here, we set up a robust in vitro immune assay using phytohemagglutinin-or anti-CD3/CD28treated human peripheral blood mononuclear cells in cell-to-cell interaction or in cellcontact independent format with UC-MSC and conducted integrated transcriptome and secretome analyses to dissect molecular pathways driving UC-MSC-mediated immune modulation. Under inflammatory stimuli, multiparametric analyses of the secretome led us to identify cytokine/chemokine expression patterns associated with the induction of MSC-reprogrammed macrophages and T cell subsets ultimately leading to immune suppression. UC-MSC transcriptome analysis under inflammatory challenge allowed the identification of 47 differentially expressed genes, including chemokines, antiand pro-inflammatory cytokines and adhesion molecules found also in UC-MSCimmunosupressive secretomes, including the novel candidate soluble IL-2R. This study enabled us to track functionally activated UC-MSC during immune suppression and opened an opportunity to explore new pathways involved in immunity control by UC-MSC. We propose that identified immunomodulatory molecules and pathways could potentially be translated into clinical settings in order to improve UC-MSC-therapy quality and efficacy.

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“…Cotransplantation of MSC was also reported to promote enhanced survival of retinal progenitor cells [ 81 ], skeletal muscle-derived stem/progenitor cells [ 70 ] and to prevent microglia activation and gliosis in the retina [ 81 ] and fibrosis in the muscular tissue [ 70 ]. Most likely these effects can be attributed to remarkable immunomodulatory/anti-inflammatory activity of MSC [ 9 , 87 , 88 ] and their angiogenic, antiapoptotic, protective, and antioxidative properties, which are mediated mainly through paracrine mechanisms (reviewed in [ 89 ]) and partly by direct cell-to-cell communications [ 90 ]. Moreover, MSC allegedly enhance cell viability through forming cell-to-cell contacts for transfer of mitochondria to damaged cells [ 90 , 91 , 92 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Cell Therapy in the Treatment of Neurological Disorders

et al. 2020

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Cell therapy of neurological diseases is gaining momentum. Various types of stem/progenitor cells and their derivatives have shown positive therapeutic results in animal models of neurological disorders and in clinical trials. Each tested cell type proved to have its advantages and flaws and unique cellular and molecular mechanism of action, prompting the idea to test combined transplantation of two or more types of cells (combined cell therapy). This review summarizes the results of combined cell therapy of neurological pathologies reported up to this point. The number of papers describing experimental studies or clinical trials addressing this subject is still limited. However, its successful application to the treatment of neurological pathologies including stroke, spinal cord injury, neurodegenerative diseases, Duchenne muscular dystrophy, and retinal degeneration has been reported in both experimental and clinical studies. The advantages of combined cell therapy can be realized by simple summation of beneficial effects of different cells. Alternatively, one kind of cells can support the survival and functioning of the other by enhancing the formation of optimum environment or immunomodulation. No significant adverse events were reported. Combined cell therapy is a promising approach for the treatment of neurological disorders, but further research needs to be conducted.

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Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors

Cited by 59 publications

References 158 publications

Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients

Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients

Integrated Analysis of Transcriptome and Secretome From Umbilical Cord Mesenchymal Stromal Cells Reveal New Mechanisms for the Modulation of Inflammation and Immune Activation

Combined Cell Therapy in the Treatment of Neurological Disorders

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