Tissue‐Related Hypoxia Attenuates Proinflammatory Effects of Allogeneic PBMCs on Adipose‐Derived Stromal Cells <i>In Vitro</i>

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

doi:10.1155/2016/4726267

Cited by 18 publications

(17 citation statements)

References 39 publications

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“…When the two cells were co‐cultured, this resulted into two switches: First, that the low BMP‐2 secretion by the MSC alone was significantly enhanced, and, second, that the high TNF‐α secretion by the monocytes alone was modestly reduced. Whereas the first finding indicates a pro‐osteogenic effect for monocytes on MSC, the relative reduction of TNF‐α in the co‐culture is in line with the prevailing hypothesis of an immunosuppressive role of MSC (Bobyleva, Andreeva, Gornostaeva, & Buravkova, ; De Miguel et al, ).…”

Section: Discussionsupporting

confidence: 78%

“…It has been suggested that interactions between MSC and immune cells are governed by factors in the local microenvironment (Bobyleva et al, ; Gornostaeva, Andreeva, & Buravkova, ). In the present study, no stimuli were added to mimic for instance the acute inflammation associated with the trauma induced during surgical insertion of an implant.…”

Section: Discussionmentioning

confidence: 99%

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Interactions between monocytes, mesenchymal stem cells, and implants evaluated using flow cytometry and gene expression

Lennerås

Ekström

Vazirisani

et al. 2018

J Tissue Eng Regen Med

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Monocytes and mesenchymal stem cells (MSC) are evident at the implants during early healing. However, when coexisting, their interactions at different implants have not been determined. This study uses an in vitro system, consisting of monoculture and direct co-cultures of monocytes and MSC on screw-shaped machined and oxidized titanium implants in combination with scanning electron microscopy, enzyme-linked immunosorbent assay, flow cytometry, cell sorting, and quantitative polymerase chain reaction. The cell-specific adhesion and gene expression of monocytes and MSC was determined. After 24 hr, the coexistence of monocytes and MSC in co-culture led to equal proportions of adherent monocytes and MSC, irrespective of the implant type. In contrast, higher number of adherent monocytes than MSC was found on the oxidized implant in monoculture. Quantitative polymerase chain reaction analysis of fluorescent activated cell sorting-sorted cells revealed up-regulation of interleukin-1beta, in monocytes, and interleukin-1beta and C-X-C chemokine receptor type 4, in MSC, when the cell types coexisted compared with monocultures. Further, in co-culture, the expression of bone morphogenetic protein-2, stromal cell-derived factor 1, and integrin-β1 was enhanced in the implant-adherent MSC, but not monocytes. It is concluded that during the first 24 hr in an in vitro static condition, the effect of co-culture of monocytes and MSC was more prominent than the effect of the implant surface properties. The results indicate that the coexistence of monocytes and MSC on an implant alters the adhesion and expression of some genes compared with when each cell type existed alone. Further, the results show that the gene expression of major growth and recruitment factors is mainly enhanced in the implant-adherent MSC in contrast to implant-adherent monocytes in co-culture.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Interactions between monocytes, mesenchymal stem cells, and implants evaluated using flow cytometry and gene expression

Lennerås

Ekström

Vazirisani

et al. 2018

J Tissue Eng Regen Med

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“…One such parameter is expansion of MSCs under hypoxia. A large number of studies demonstrated that MSCs cultured in hypoxia exhibit higher rates of proliferation and better retain their stem cell properties [ 25 , 30 – 33 ]. Yet, some studies reported conflicting results showing negative or no effects on MSCs by hypoxia [ 34 – 36 ].…”

Section: Introductionmentioning

confidence: 99%

Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells

et al. 2018

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BackgroundIn the bone marrow, MSCs reside in a hypoxic milieu (1–5% O2) that is thought to preserve their multipotent state. Typically, in vitro expansion of MSCs is performed under normoxia (~ 21% O2), a process that has been shown to impair their function. Here, we evaluated the characteristics and function of MSCs cultured under hypoxia and hypothesized that, when compared to normoxia, dedicated hypoxia will augment the functional characteristics of MSCs.MethodsHuman and porcine bone marrow MSCs were obtained from fresh mononuclear cells. The first study evaluated MSC function following both long-term (10 days) and short-term (48 h) hypoxia (1% O2) culture. In our second study, we evaluated the functional characteristics of MSC cultured under short-term 2% and 5% hypoxia. MSCs were evaluated for their metabolic activity, proliferation, viability, clonogenicity, gene expression, and secretory capacity.ResultsIn long-term culture, common MSC surface marker expression (CD44 and CD105) dropped under hypoxia. Additionally, in long-term culture, MSCs proliferated significantly slower and provided lower yields under hypoxia. Conversely, in short-term culture, MSCs proliferated significantly faster under hypoxia. In both long-term and short-term cultures, MSC metabolic activity was significantly higher under hypoxia. Furthermore, MSCs cultured under hypoxia had upregulated expression of VEGF with concomitant downregulation of HMGB1 and the apoptotic genes BCL-2 and CASP3. Finally, in both hypoxia cultures, the pro-inflammatory cytokine, IL-8, was suppressed, while levels of the anti-inflammatories, IL-1ra and GM-CSF, were elevated in short-term hypoxia only.ConclusionsIn this study, we demonstrate that hypoxia augments the therapeutic characteristics of both porcine and human MSCs. Yet, short-term 2% hypoxia offers the greatest benefit overall, exemplified by the increase in proliferation, self-renewing capacity, and modulation of key genes and the inflammatory milieu as compared to normoxia. These data are important for generating robust MSCs with augmented function for clinical applications.

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“…16 It is reasonable to assume that a direct cell-cell interaction leads to a more significant effect on cellular activity (due to both the close direct contacts and the effect of higher paracrine factor levels in the pericellular milieu). This change apparently includes the upregulation of matrix degradation genes and downregulation of certain extracellular matrix and regulatory molecule genes.…”

mentioning

confidence: 99%

“…This change apparently includes the upregulation of matrix degradation genes and downregulation of certain extracellular matrix and regulatory molecule genes. 16 It is reasonable to assume that a direct cell-cell interaction leads to a more significant effect on cellular activity (due to both the close direct contacts and the effect of higher paracrine factor levels in the pericellular milieu). Indeed, a number of studies demonstrated increased MSC immunosuppressive activity upon their direct contact with activated immune cells.…”

mentioning

confidence: 99%

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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Tissue‐Related Hypoxia Attenuates Proinflammatory Effects of Allogeneic PBMCs on Adipose‐Derived Stromal Cells In Vitro

Cited by 18 publications

References 39 publications

Interactions between monocytes, mesenchymal stem cells, and implants evaluated using flow cytometry and gene expression

Interactions between monocytes, mesenchymal stem cells, and implants evaluated using flow cytometry and gene expression

Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells

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

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