scholarly journals Injection of Adipose-Derived Stromal Cells in the Knee of Patients with Severe Osteoarthritis has a Systemic Effect and Promotes an Anti-Inflammatory Phenotype of Circulating Immune Cells

Theranostics ◽  
2018 ◽  
Vol 8 (20) ◽  
pp. 5519-5528 ◽  
Author(s):  
Yves-Marie Pers ◽  
Julie Quentin ◽  
Rosanna Feirreira ◽  
Francisco Espinoza ◽  
Naoill Abdellaoui ◽  
...  
Keyword(s):  
Immune Cells ◽  
Stromal Cells ◽  
Systemic Effect ◽  
Adipose Derived Stromal Cells ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

scholarly journals ID2006 Crosstalk between effector cells of adaptive immunity and mesenchymal stromal cells

2017 ◽  
Vol 4 (S) ◽  
pp. 38
Author(s):  
Aleksandra Gornostaeva
Keyword(s):  
Innate Immunity ◽  
Adaptive Immunity ◽  
Mesenchymal Stromal Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Feedback Loop ◽  
Inflammatory Phenotype ◽  
Innate Immunity Cells ◽  
Immunomodulatory Properties ◽  
Anti Inflammatory

Multipotent mesenchymal stromal cells (MSCs) are a perspective tool for regenerative medicine due low immunogenicity and immunomodulation. The "feedback loop" exists in MSC/immune cells relationships, when "inflammatory" stimulation switches immunoregulaton by MSCs. Currently, the most studied effect of allogeneic MSCs on adaptive immunity cells, mainly on T lymphocytes. Studies of the interaction of MSCs and innate immunity cells are much less. "Reverse effects" (the effect of immune cells on MSCs) are virtually not investigated. Initiation of the inflammation occurs with activation of innate immunity cells, that "turns on" immunomodulatory properties. In this regard, the study of the interaction of MSCs and monocytes is particularly relevant. MSCs from human adipose tissue and CD14+monocytes (MNs) from peripheral blood of healthy volunteers were used. To stimulate monocytes conditioned medium (CM) after 72 hours of mixed lymphocyte reaction (MLR) was applied. This CM was enriched with IL-8, INF-gamma and TNF-a.  Optimization of MN activation procedure was performed prior to experiments. CD14+MNs were incubated with different concentration of MLR-CM for a different time. The activation and viability of MNs was evaluated every 24 hours. The overnight exposure of MNs to 3-day 50% CM-MLR was found to be optimum regime. We studied the of MSC/monocyte interaction paying special attention to "feedback loop".  In the presence of activated MNs, MSCs possessed unchanged viability (96%), transmembrane mitochondria potential, ROS level and twice reduced lysosome activity. The cytokine profile in coculture medium was changed significantly. IL-6 and MCP-1 were increased vs monocultures of both cell types. IL-8 was similar to MN monoculture. TNF alpha, MIG, IL-10 were detected as tracers. Elevation of IL-6 and MIG indicates on acquisition of anti-inflammatory phenotype by MSCs. After interaction with MSC, the share of CD69+ MNs (nonspecific marker of early activation) decreased, HLA-DR (MHC class II receptor) increased slightly. A threefold increase in both CD163+ MN’s share and MFI was detected, whereas CD86 antigen was not expressed. The changes in the cytokine profile and the expression of surface markers described above are characteristic of the anti-inflammatory phenotype of monocytes.  Thus, upon interaction MSC exhibited pronounced immunomodulatory properties and shifted the phenotype of monocytes towards the anti-inflammatory. These data indicate on the MSC potential to modulate early stages of inflammation, while retaining their functional state.

scholarly journals Tumor-Associated Macrophage Status in Cancer Treatment

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1987 ◽  
Author(s):  
Anna Maria Malfitano ◽  
Simona Pisanti ◽  
Fabiana Napolitano ◽  
Sarah Di Somma ◽  
Rosanna Martinelli ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Cells ◽  
Indirect Effects ◽  
Poor Prognosis ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Tumor Associated Macrophage ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
Activation Status

Tumor-associated macrophages (TAMs) represent the most abundant innate immune cells in tumors. TAMs, exhibiting anti-inflammatory phenotype, are key players in cancer progression, metastasis and resistance to therapy. A high TAM infiltration is generally associated with poor prognosis, but macrophages are highly plastic cells that can adopt either proinflammatory/antitumor or anti-inflammatory/protumor features in response to tumor microenvironment stimuli. In the context of cancer therapy, many anticancer therapeutics, apart from their direct effect on tumor cells, display different effects on TAM activation status and density. In this review, we aim to evaluate the indirect effects of anticancer therapies in the modulation of TAM phenotypes and pro/antitumor activity.

scholarly journals Glucocorticoid receptor in stromal cells is essential for glucocorticoid-mediated suppression of inflammation in arthritis

2018 ◽  
Vol 77 (11) ◽  
pp. 1610-1618 ◽  
Author(s):  
Mascha Koenen ◽  
Stephan Culemann ◽  
Sabine Vettorazzi ◽  
Giorgio Caratti ◽  
Lucien Frappart ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Immune Cells ◽  
Stromal Cells ◽  
Gene Signature ◽  
Stromal Compartment ◽  
Inflammatory Protein ◽  
Inflammatory Mechanism ◽  
Efficient Suppression ◽  
Murine Fibroblast ◽  
Anti Inflammatory

BackgroundGlucocorticoid (GC) therapy is frequently used to treat rheumatoid arthritis due to potent anti-inflammatory actions of GCs. Direct actions of GCs on immune cells were suggested to suppress inflammation.ObjectivesDefine the role of the glucocorticoid receptor (GR) in stromal cells for suppression of inflammatory arthritis.MethodsBone marrow chimeric mice lacking the GR in the hematopoietic or stromal compartment, respectively, and mice with impaired GR dimerisation (GRdim) were analysed for their response to dexamethasone (DEX, 1 mg/kg) treatment in serum transfer-induced arthritis (STIA). Joint swelling, cell infiltration (histology), cytokines, cell composition (flow cytometry) and gene expression were analysed and RNASeq of wild type and GRdim primary murine fibroblast-like synoviocytes (FLS) was performed.ResultsGR deficiency in immune cells did not impair GC-mediated suppression of STIA. In contrast, mice with GR-deficient or GR dimerisation-impaired stromal cells were resistant to GC treatment, despite efficient suppression of cytokines. Intriguingly, in mice with impaired GR function in the stromal compartment, GCs failed to stimulate non-classical, non-activated macrophages (Ly6Cneg, MHCIIneg) and associated anti-inflammatory markers CD163, CD36, AnxA1, MerTK and Axl. Mice with GR deficiency in FLS were partially resistant to GC-induced suppression of STIA. Accordingly, RNASeq analysis of DEX-treated GRdim FLS revealed a distinct gene signature indicating enhanced activity and a failure to reduce macrophage inflammatory protein (Mip)-1α and Mip-1β.ConclusionWe report a novel anti-inflammatory mechanism of GC action that involves GR dimerisation-dependent gene regulation in non-immune stromal cells, presumably FLS. FLS control non-classical, anti-inflammatory polarisation of macrophages that contributes to suppression of inflammation in arthritis.

scholarly journals Bone Marrow-Derived Mesenchymal Stromal Cells (MSCs) Modulate the Inflammatory Character of Alveolar Macrophages from Sarcoidosis Patients

2020 ◽  
Vol 9 (1) ◽  
pp. 278 ◽  
Author(s):  
Ian McClain Caldwell ◽  
Christopher Hogden ◽  
Krisztian Nemeth ◽  
Michael Boyajian ◽  
Miklos Krepuska ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Mesenchymal Stromal Cells ◽  
Alveolar Macrophages ◽  
Stromal Cells ◽  
Cultured Cells ◽  
Intracellular Cytokines ◽  
Tnf Α ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Sarcoidosis is a devastating inflammatory disease affecting many organs, especially the lungs and lymph nodes. Bone marrow-derived mesenchymal stromal cells (MSCs) can “reprogram” various types of macrophages towards an anti-inflammatory phenotype. We wanted to determine whether alveolar macrophages from sarcoidosis subjects behave similarly by mounting an anti-inflammatory response when co-cultured with MSCs. Fifteen sarcoidosis and eight control subjects underwent bronchoscopy and bronchoalveolar lavage (BAL). Unselected BAL cells (70–94% macrophages) were isolated and cultured with and without MSCs from healthy adults. Following stimulation of the cultured cells with lipopolysaccharide, the medium was removed to measure interleukin 10 and tumor necrosis factor alpha (IL-10 and TNF-α). In two additional sarcoidosis subjects, flow cytometry was used to study intracellular cytokines and surface markers associated with alveolar macrophages to confirm the results. Unselected BAL cells from sarcoidosis subjects co-cultured with MSCs showed a reduction in TNF-α (pro-inflammatory M1) and an increase in IL-10 (anti-inflammatory M2) in 9 of 11 samples studied. Control subject samples showed few, if any, differences in cytokine production. Unselected BAL cells from two additional patients analyzed by flow cytometry confirmed a switch towards an anti-inflammatory state (i.e., M1 to M2) after co-culture with MSCs. These results suggest that, similarly to other macrophages, alveolar macrophages also respond to MSC contacts by changing towards an anti-inflammatory phenotype. Based on our results, we hypothesize that mesenchymal stromal cells applied to the airways might alleviate lung inflammation and decrease steroid need in patients with sarcoidosis.

EFFECT OF MULTIPOTENT MESENCHYMAL STROMAL CELLS ON THE FUNCTIONAL ACTIVITY OF MONOCYTE-DERIVED MACROPHAGES UNDER A SHORT-TERM HYPOXIC STRESS IN VITRO

2021 ◽  
Vol 55 (5) ◽  
pp. 45-52
Author(s):  
O.Yu. Alekseeva ◽  
◽  
P.I. Bobyleva ◽  
E.R. Andreeva ◽  
◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Functional Activity ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Hypoxic Stress ◽  
Hypoxic Conditions ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

We studied interactions of mesenchymal stromal cells (MSCs) and cells from the monocyte-macrophage group (MN/MP) important in the MSCs mediated therapeutic action in vivo, their anti-inflammatory and immunomodulating properties. The MSCs effect on the MN/MP functional activity was evaluated after a 6-d co-culture in standard conditions (20 % О2) and ensuing exposure of one part of MN/MP and MN/MP+MSCs to a long-term hypoxic stress (1 % О2, 24 hrs) while the other part remained at 20 % О2. As in the normal, so hypoxic conditions the MSCs stromal activity contributed to the MN/MP viability by decreasing the numbers of MN/MP cells during early apoptosis. The paracrine interaction in 20 % О2 occurred with an elevated MN/MP phagocytic activity without influence on the lysosomal compartment activity. The hypoxic stress affected the MSCs-induced phagocytic ability and activity of lysosomes. Interaction with MSCs leads to formation of a MN/MP anti-inflammatory phenotype that unveils the phagocytic potential in the presence of MSCs despite the oxygen deprivation.

scholarly journals Vascular and Macrophage Heme Oxygenase-1 in Hypertension: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Martínez-Casales ◽  
Raquel Hernanz ◽  
María J. Alonso
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Immune Cells ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Heme Oxygenase 1 ◽  
Ischemic Disease ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Hypertension is one predictive factor for stroke and heart ischemic disease. Nowadays, it is considered an inflammatory disease with elevated cytokine levels, oxidative stress, and infiltration of immune cells in several organs including heart, kidney, and vessels, which contribute to the hypertension-associated cardiovascular damage. Macrophages, the most abundant immune cells in tissues, have a high degree of plasticity that is manifested by polarization in different phenotypes, with the most well-known being M1 (proinflammatory) and M2 (anti-inflammatory). In hypertension, M1 phenotype predominates, producing inflammatory cytokines and oxidative stress, and mediating many mechanisms involved in the pathogenesis of this disease. The increase in the renin–angiotensin system and sympathetic activity contributes to the macrophage mobilization and to its polarization to the pro-inflammatory phenotype. Heme oxygenase-1 (HO-1), a phase II detoxification enzyme responsible for heme catabolism, is induced by oxidative stress, among others. HO-1 has been shown to protect against oxidative and inflammatory insults in hypertension, reducing end organ damage and blood pressure, not only by its expression at the vascular level, but also by shifting macrophages toward the anti-inflammatory phenotype. The regulatory role of heme availability for the synthesis of enzymes involved in hypertension development, such as cyclooxygenase or nitric oxide synthase, seems to be responsible for many of the beneficial HO-1 effects; additionally, the antioxidant, anti-inflammatory, antiapoptotic, and antiproliferative effects of the end products of its reaction, carbon monoxide, biliverdin/bilirubin, and Fe2+, would also contribute. In this review, we analyze the role of HO-1 in hypertensive pathology, focusing on its expression in macrophages.

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