scholarly journals Human Mesenchymal Stem/Stromal Cells Cultured as Spheroids are Self-activated to Produce Prostaglandin E2 that Directs Stimulated Macrophages into an Anti-inflammatory Phenotype

Stem Cells ◽  
2012 ◽  
Vol 30 (10) ◽  
pp. 2283-2296 ◽  
Author(s):  
Joni H. YlÖstalo ◽  
Thomas J. Bartosh ◽  
Katie Coble ◽  
Darwin J. Prockop
Theranostics ◽  
2018 ◽  
Vol 8 (20) ◽  
pp. 5519-5528 ◽  
Author(s):  
Yves-Marie Pers ◽  
Julie Quentin ◽  
Rosanna Feirreira ◽  
Francisco Espinoza ◽  
Naoill Abdellaoui ◽  
...  

2015 ◽  
Vol 45 (9) ◽  
pp. 2661-2671 ◽  
Author(s):  
Yi Rang Na ◽  
Daun Jung ◽  
Bo Ruem Yoon ◽  
Won Woo Lee ◽  
Seung Hyeok Seok

2020 ◽  
Vol 9 (1) ◽  
pp. 278 ◽  
Author(s):  
Ian McClain Caldwell ◽  
Christopher Hogden ◽  
Krisztian Nemeth ◽  
Michael Boyajian ◽  
Miklos Krepuska ◽  
...  

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.


2021 ◽  
Vol 55 (5) ◽  
pp. 45-52
Author(s):  
O.Yu. Alekseeva ◽  
◽  
P.I. Bobyleva ◽  
E.R. Andreeva ◽  
◽  
...  

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.


2017 ◽  
Vol 4 (S) ◽  
pp. 38
Author(s):  
Aleksandra Gornostaeva

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.


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