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

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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A Review of Antimicrobial Activity of Dental Mesenchymal Stromal Cells: Is There Any Potential?

Frontiers in Oral Health ◽

10.3389/froh.2021.832976 ◽

2022 ◽

Vol 2 ◽

Author(s):

Oleh Andrukhov ◽

Alice Blufstein ◽

Christian Behm

Keyword(s):

Vitamin D ◽

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Mesenchymal Stromal Cells ◽

Immune Cells ◽

Stromal Cells ◽

Multilineage Differentiation ◽

Differentiation Potential ◽

Health Maintenance ◽

Immunomodulatory Properties

Antimicrobial defense is an essential component of host-microbial homeostasis and contributes substantially to oral health maintenance. Dental mesenchymal stromal cells (MSCs) possess multilineage differentiation potential, immunomodulatory properties and play an important role in various processes like regeneration and disease progression. Recent studies show that dental MSCs might also be involved in antibacterial defense. This occurs by producing antimicrobial peptides or attracting professional phagocytic immune cells and modulating their activity. The production of antimicrobial peptides and immunomodulatory abilities of dental MSCs are enhanced by an inflammatory environment and influenced by vitamin D3. Antimicrobial peptides also have anti-inflammatory effects in dental MSCs and improve their differentiation potential. Augmentation of antibacterial efficiency of dental MSCs could broaden their clinical application in dentistry.

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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 ◽

10.7150/thno.27674 ◽

2018 ◽

Vol 8 (20) ◽

pp. 5519-5528 ◽

Cited By ~ 13

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

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Mesenchymal Stromal Cells and Their Extracellular Vesicles Enhance the Anti-Inflammatory Phenotype of Regulatory Macrophages by Downregulating the Production of Interleukin (IL)-23 and IL-22

Frontiers in Immunology ◽

10.3389/fimmu.2018.00771 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 26

Author(s):

Kati Hyvärinen ◽

Minna Holopainen ◽

Vita Skirdenko ◽

Hanna Ruhanen ◽

Petri Lehenkari ◽

...

Keyword(s):

Extracellular Vesicles ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Inflammatory Phenotype ◽

Anti Inflammatory

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A novel, non-genetic, and scalable proprietary method for enhancing anti-inflammatory, and immunomodulatory properties of mesenchymal stromal cells (MSCs) prior to cryopreservation

Cytotherapy ◽

10.1016/j.jcyt.2018.02.073 ◽

2018 ◽

Vol 20 (5) ◽

pp. S29

Author(s):

S. Bhatt ◽

A. Gómez-Aristizábal ◽

J. Whiteley ◽

I. Rogers ◽

S. Viswanathan

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Immunomodulatory Properties ◽

Anti Inflammatory

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

Journal of Clinical Medicine ◽

10.3390/jcm9010278 ◽

2020 ◽

Vol 9 (1) ◽

pp. 278 ◽

Cited By ~ 4

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.

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

Aerospace and Environmental Medicine ◽

10.21687/0233-528x-2021-55-5-45-52 ◽

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.

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The use of mesenchymal stromal cells in the treatment of coronavirus disease 2019

Journal of Translational Medicine ◽

10.1186/s12967-020-02532-4 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Maurice A. Canham ◽

John D. M. Campbell ◽

Joanne C. Mountford

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Immune Response ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Host Response ◽

Distress Syndrome ◽

Graft Versus Host ◽

Immunomodulatory Properties ◽

Efficacious Vaccine

Abstract More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.

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