In vitro assessment of mesenchymal stem cells immunosuppressive potential in multiple sclerosis patients

Zafranskaya, Marina; Nizheharodova, Darya B.; Yurkevich, M.; Lamouskaya, Natallia V.; Motuzova, Yana; Багатка, С. С.; Ivanchik, Halina I.; Федулов, А. С.

doi:10.1016/j.imlet.2012.10.010

Cited by 16 publications

(10 citation statements)

References 70 publications

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“…, Table ) that corresponds to the results of other authors . rMOG was used as in vitro potential target autoantigen and as the most immunogenic and acceptable protein for assessing the intensity of cellular and humoral reactions in MS according to our previous data . According to this study, inhibitory effects of allogeneic as well as autologous MSC from patients with MS on myelin‐specific T cell proliferation were more expressed as compared to the analysed data in healthy donors (Fig.…”

Section: Discussionsupporting

confidence: 74%

“…Cell culture supernatants (medium conditioned by cell cultures) were obtained from subconfluent MSC cultures (passages 1–2) 72 h after the medium was changed and then used in proliferation assay and for estimating PGE 2 concentration. To confirm a multilineage differentiation potential, confluent MSC cultures (passage 1–2) were cultured in adipogenic and osteogenic differentiation media for 4 weeks as previously described .…”

Section: Methodsmentioning

confidence: 99%

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PGE₂ Contributes to In vitro MSC‐Mediated Inhibition of Non‐Specific and Antigen‐Specific T Cell Proliferation in MS Patients

et al. 2013

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Current theories of multiple sclerosis (MS) induction and progression place autoreactive T cells in the focus of the pathogenesis. Mesenchymal/stromal stem cells (MSC) have become a promising alternative approach for pathogenic therapy of MS due to their immunomodulatory properties, underlying mechanisms of which are intensive study. The objective of the research was to investigate the contribution of PGE 2 to MSC-mediated suppression in patients with MS using in vitro model of mitogen-and myelin-stimulated T cell cocultivation with autologous/allogeneic MSC. We have showed that PGE 2 production depends on cell-to-cell contact of MSC and lymphocytes. The antigenic stimulation did not affect PGE 2 production following cocultivation of MSC and PBMC, and it is the presence of MSC in cell culture that significantly increases PGE 2 production irrespective of antigenic cultivation conditions. Simultaneously, PGE 2 synthesis correlated with indexes of MSC-mediated suppression of mitogen-and myelinstimulated T cell proliferation in patients with MS. No significant differences in PGE 2 production by autologous and allogeneic MSC have been established. These results have demonstrated that in patients with MS, PGE 2 is one of the possible factors of MSC immunosuppression. The interrelation between PGE 2 concentrations and T cell proliferation suppression mediated by MSC may explain one of the immune mechanisms of cell therapy, which is crucial for the further proper use of MSC in MS research and pathogenic treatment.

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Section: Discussionsupporting

confidence: 74%

Section: Methodsmentioning

confidence: 99%

PGE₂ Contributes to In vitro MSC‐Mediated Inhibition of Non‐Specific and Antigen‐Specific T Cell Proliferation in MS Patients

et al. 2013

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“…Following a T-cell-based approach to determine the immunosuppressive capacity of MSCs, Zafranskaya et al suggested the analysis of CD119 expression of myelin-induced memory Tcells as a means to anticipate the efficacy of MSC therapy in multiple sclerosis patients [46]. Using a different approach, we addressed features of MSCs themselves to find surrogate markers as substitutes for the time-consuming and error-susceptible T-cell proliferation assay.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive capabilities of mesenchymal stromal cells are maintained under hypoxic growth conditions and after gamma irradiation

et al. 2015

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“…Promising therapeutic effects have been reported in autoimmune disorders [3], in particular for treatment of multiple sclerosis and graft-versus-host disease (GvHD) [4–7]. …”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive capacity of mesenchymal stem cells correlates with metabolic activity and can be enhanced by valproic acid

Killer¹,

Nold²,

Henkenius³

et al. 2017

Stem Cell Res Ther

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BackgroundMesenchymal stem cells (MSCs) have entered the clinic as an Advanced Therapy Medicinal Product and are currently evaluated in a wide range of studies for tissue regeneration or in autoimmune disorders. Various efforts have been made to standardize and optimize expansion and manufacturing processes, but until now reliable potency assays for the final MSC product are lacking. Because recent findings suggest superior therapeutic efficacy of freshly administered MSCs in comparison with frozen cells, we sought to correlate the T-cell suppressive capacity of MSCs with their metabolic activity.MethodsHuman MSCs were obtained from patients’ bone fragments and were employed in coculture with peripheral blood mononuclear cells (PBMCs) in an allogeneic T-cell proliferation assay to measure immunosuppressive function. Metabolic activity of MSCs was measured in real time in terms of aerobic glycolysis quantified by the extracellular acidification rate and mitochondrial respiration quantified by the oxygen consumption rate.ResultsWe show that MSC-induced suppression of T-cell proliferation was highly dependent on individual healthy donors’ lymphocytes. Moreover, coculture with PBMCs increased the glycolytic and respiratory activity of MSCs considerably in a PBMC donor-dependent manner. The twofold to threefold enhancement of cell metabolism was accompanied by higher T-cell suppressive capacities of MSCs. The cryoprotectant dimethyl sulfoxide decreased metabolic and immunosuppressive performances of MSCs while valproic acid (VPA) increased their glycolytic, respiratory and T-cell suppressive capacity.ConclusionsFunctional fitness of MSCs can be determined by measuring metabolic activity and can be enhanced by exposure to VPA. Pretesting the increment of metabolic activity upon interaction of donor MSCs with patient T-cells provides a rational approach for an individualized potency assay prior to MSC therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0553-y) contains supplementary material, which is available to authorized users.

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In vitro assessment of mesenchymal stem cells immunosuppressive potential in multiple sclerosis patients

Cited by 16 publications

References 70 publications

PGE₂ Contributes to In vitro MSC‐Mediated Inhibition of Non‐Specific and Antigen‐Specific T Cell Proliferation in MS Patients

PGE₂ Contributes to In vitro MSC‐Mediated Inhibition of Non‐Specific and Antigen‐Specific T Cell Proliferation in MS Patients

Immunosuppressive capabilities of mesenchymal stromal cells are maintained under hypoxic growth conditions and after gamma irradiation

Immunosuppressive capacity of mesenchymal stem cells correlates with metabolic activity and can be enhanced by valproic acid

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In vitro assessment of mesenchymal stem cells immunosuppressive potential in multiple sclerosis patients

Cited by 16 publications

References 70 publications

PGE2 Contributes to In vitro MSC‐Mediated Inhibition of Non‐Specific and Antigen‐Specific T Cell Proliferation in MS Patients

PGE2 Contributes to In vitro MSC‐Mediated Inhibition of Non‐Specific and Antigen‐Specific T Cell Proliferation in MS Patients

Immunosuppressive capabilities of mesenchymal stromal cells are maintained under hypoxic growth conditions and after gamma irradiation

Immunosuppressive capacity of mesenchymal stem cells correlates with metabolic activity and can be enhanced by valproic acid

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PGE₂ Contributes to In vitro MSC‐Mediated Inhibition of Non‐Specific and Antigen‐Specific T Cell Proliferation in MS Patients

PGE₂ Contributes to In vitro MSC‐Mediated Inhibition of Non‐Specific and Antigen‐Specific T Cell Proliferation in MS Patients