Human MMSC immunosuppressive activity at low oxygen tension: Direct cell-to-cell contacts and paracrine regulation

Горностаева, А. Н.; Andreeva, E. R.; Буравкова, Л. Б.

doi:10.1134/s0362119713020059

Cited by 12 publications

(23 citation statements)

References 51 publications

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“…(Suva et al 2008;Yang et al 2009;Andreeva et al 2012;Engela et al 2012;Francois et al 2012;Gornostaeva et al 2013). However, the analysis of the broad spectrum of data discloses the dissimilarity and contradiction in the reported results, when suppressive, as well as stimulating, effects were described (Grigoryan et al 2007;Crop et al 2010;Saldanha-Araujo et al 2012).…”

Section: Introductioncontrasting

confidence: 69%

“…On the contrary, IFN-c synthesis increased in the co-culture of MSCs and aCD3/aCD28-stimulated lymphocytes (Kronsteiner et al 2011). According to our data, in the presence of MSCs, the IFN-c and IL-10 production by PHA-stimulated lymphocytes increased and TNF-a decreased (Gornostaeva et al 2011(Gornostaeva et al , 2013. In the co-culture with MSCs, the CD3/CD28-activated T-cells demonstrated a significant increase in apoptotic cells (Yang et al 2009;Park et al 2011); at the same time, the share of apoptotic cells did not change among ConA and PHA-stimulating lymphocytes (Zappia et al 2005;Gornostaeva et al 2011Gornostaeva et al , 2013.…”

Section: Activation Of Immune Cellsmentioning

confidence: 49%

“…Suppression of MLR-activated cells was distinct only when the MSCs/lymphocytes ratio was as high as 1:1, 1:2 and 1:4 (McIntosh et al 2006). Our findings show that MSCs are capable of effectively suppressing the proliferation of PHA-stimulated lymphocytes at the ratio of 1:10 (Gornostaeva et al 2011(Gornostaeva et al , 2013 (Table 1).…”

Section: Mscs/immune Cells Ratiomentioning

confidence: 73%

“…The same relationship was observed in the absence of a direct cell contact between MSCs and T-cells (Suva et al 2008). According to others, MSCs were able to suppress lymphocyte proliferation effectively when only PHA was used for activation (Puissant et al 2005;Kronsteiner et al 2011;Gornostaeva et al 2011Gornostaeva et al , 2013.…”

Section: Activation Of Immune Cellsmentioning

confidence: 96%

“…In our lab we performed a comparative analysis of the immunosuppressive effects of the adhered and suspended MSCs. It turned out that suspended cells have a stronger antiproliferative effect on the T-lymphocytes, but their ability to down-regulate lymphocyte activation does not differ from that of adhered MSCs (Gornostaeva et al 2011(Gornostaeva et al , 2013.…”

Section: Culture Conditions and Msc Immunosuppressionmentioning

confidence: 96%

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Factors governing the immunosuppressive effects of multipotent mesenchymal stromal cells in vitro

2015

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Multipotent mesenchymal stem/stromal cells (MSCs) are of great interest to researchers because of the unique properties, such as enhanced proliferation, paracrine activity and multilineage differentiation. Their non-immunogenicity, in combination with immunomodulatory properties, opens up the opportunity for the allogeneic application of MSCs. The MSC immunomodulatory capacity is currently being actively studied in vitro using various experimental designs. However, the results are not always univocal. It was found that the outcome of the stromal/immune cell interaction depends on experimental conditions. In this review we considered the impact of different factors, such as the ratio of stromal/immune cells, interaction time, the path of immune cell activation, etc. on the MSC immunomodulation. We also accentuated the importance of local milieu, in particular, oxygen tension, for the realization of MSC immunosuppressive activity.

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Section: Introductioncontrasting

confidence: 69%

Section: Activation Of Immune Cellsmentioning

confidence: 49%

Section: Mscs/immune Cells Ratiomentioning

confidence: 73%

Section: Activation Of Immune Cellsmentioning

confidence: 96%

Section: Culture Conditions and Msc Immunosuppressionmentioning

confidence: 96%

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Factors governing the immunosuppressive effects of multipotent mesenchymal stromal cells in vitro

2015

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Proinflammatory interleukins' production by adipose tissue‐derived mesenchymal stromal cells: the impact of cell culture conditions and cell‐to‐cell interaction

Andreeva

Андрианова

Rylova

et al. 2015

Cell Biochemistry & Function

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The impact of culture conditions and interaction with activated peripheral blood mononuclear cells on the interleukin (IL) gene expression profile and proinflammatory IL-6 and IL-8 production by adipose-derived stromal cells (ASCs) was investigated. A microarray analysis revealed a wide range of IL genes either under standard (20%) or hypoxic (5%) O2 concentrations, some highly up-regulated at hypoxia. IL-6 and IL-8 production was inversely dependent on cell culture density. In early (first-third) passages, IL-6 and IL-8 concentration was higher at 20% O2 and in late (8th-12th) passages under 5% O2. Interaction between ASCs and mononuclear cells in indirect setting was accompanied with a significant decrease of IL-6 and did not result in the elevation of IL-8 concentration. Thereby, the production of proinflammatory interleukins (IL-6 and IL-8) may be affected by the ASC intrinsic features (density in culture, and duration of expansion), as well as by microenvironmental factors, such as hypoxia and the presence of blood-borne cells. These data are important for elucidating ASC paracrine activity regulation in vitro. They would also be on demand for optimisation of the cell therapy protocols, based on the application of ASC biologically active substances. SIGNIFICANCE PARAGRAPH: Ex vivo expansion is widely used for increasing the number of adipose-derived stromal cells (ASCs) and improving of their quality. The present study was designed to elucidate the particular factors influencing the interleukin production in ASCs. The presented data specified the parameters (i.e. cell density, duration of cultivation, hypoxia, etc.) that should be taken in mind when ASCs are intended to be used in protocols implying their paracrine activity. These data would be of considerable interest for researchers and clinicians working in the biomedical science.

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Reciprocal modulation of cell functions upon direct interaction of adipose mesenchymal stromal and activated immune cells

Бобылева

Горностаева

Andreeva

et al. 2019

Cell Biochemistry & Function

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The interaction of adipose mesenchymal stromal cells (ASCs) and allogeneic peripheral blood mononuclear cells (PBMCs) is regulated either through direct or paracrine mechanisms. Here, we examined the impact of direct contact in reciprocal regulation of ASC-PBMC functions. Activated PBMCs in vitro induced ASC immunomodulatory activity, while direct and paracrine intercellular interactions regulated PBMCs themselves: the functional state of the organelles was altered, and activation decreased.Direct contact with immune cells affected the activity of ASC intracellular compartments, in particular, reactive oxygen species (ROS) production, and decreased the growth rate. Some ASC properties, including motility, intercellular adhesion molecule-1 (ICAM-1), and major histocompatibility complex class I and II antigens (HLA-ABC and HLA-DR, respectively) expression, did not depend on contact with PBMCs and were only regulated by paracrine means. Direct ASC and PBMC contact favoured an angiogenesis-supportive microenvironment, possibly due to the greater production of VEGF by ASCs; this microenvironment also contained a higher leukemia inhibitory factor (LIF) level. Thus, a change in the functional activity of ASCs and PBMCs upon interaction promoted the formation of an immunosuppressive, anti-inflammatory, and proangiogenic microenvironment. This environment could help resolve inflammation and further restore damaged tissue.Significance of the study: Numerous studies have demonstrated the beneficial effects of transplanted mesenchymal stromal cells, particularly ASCs, for the treatment of a number of autoimmune diseases as well as various tissue injuries. To improve the efficiency of these methods, it is necessary to understand the principal events that occur when ASCs are introduced, primarily the molecular mechanisms of interaction between ASCs and the recipient immune system. We demonstrated that an anti-inflammatory, immunosuppressive, and angiostimulatory shift in the paracrine profile upon the interaction of activated PBMCs and ASCs changes the functional activity of both cell types, a phenomenon that is potentiated by direct cell-cell contact.KEYWORDS allogeneic interaction, direct and paracrine cell-cell interaction, human adipose tissue-derived stromal cells, immunomodulation, peripheral blood mononuclear cells

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Human MMSC immunosuppressive activity at low oxygen tension: Direct cell-to-cell contacts and paracrine regulation

Cited by 12 publications

References 51 publications

Factors governing the immunosuppressive effects of multipotent mesenchymal stromal cells in vitro

Factors governing the immunosuppressive effects of multipotent mesenchymal stromal cells in vitro

Proinflammatory interleukins' production by adipose tissue‐derived mesenchymal stromal cells: the impact of cell culture conditions and cell‐to‐cell interaction

Reciprocal modulation of cell functions upon direct interaction of adipose mesenchymal stromal and activated immune cells

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