Liraglutide has potent anti-inflammatory and anti-catabolic activity in two cell-types implicated in osteoarthritis

2021 ◽  
Vol 29 ◽  
pp. S360
Author(s):  
F. Berenbaum ◽  
C. Meurot ◽  
L. Sudre ◽  
K. Bismuth ◽  
R. Rattenbach ◽  
...  
Keyword(s):  
Cell Types ◽  
Catabolic Activity ◽  
Anti Inflammatory

Abstract 17093: Human Neonatal Cardiac Mesenchymal Stem Cells Demonstrates Superior Cardiac Regenerative Abilities Compared to Other Stem Cells

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Muthukumar Gunasekaran ◽  
Rachana Mishra ◽  
Progyaparamita Saha ◽  
Xuebin Fu ◽  
Mohamed Abdullah ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Inflammatory Cytokines ◽  
Cell Types ◽  
Wild Type ◽  
Cell Type ◽  
Anti Inflammatory ◽  
Stem Cell Type

Stem cells transplantation is being explored as an effective therapy for heart diseases. However, majority of stem cell therapies for adult patients with myocardial infarction (MI) had mixed and inconsistent results implying chronological age may influence the effectiveness of regenerative therapies. Therefore, herein, we performed a head-to-head comparison between different, well-studied stem cell types to identify the superior regenerative cell type using rodent MI model.After our standard characterization for each stem cell type (FACS for cell surface markers), 1 million neonatal Cardiac Mesenchymal Stem cells (nMSCs), adult MSCs (aMSCs), adult derived cardiosphere derived cells (aCDCs), umbilical cord derived cells (UCBCs), Bone Marrow derived Mesenchymal Stem cells (BM-MSCs), or cell-free Iscove Modified Dulbecco Medium (IMDM as placebo control) were injected into athymic rat myocardial infarct model. Although all the tested groups significantly improved ejection fraction, nMSCs outperformed other stem cells in cardiac functional recovery. Additionally, nMSCs also showed significant increased cardiac functional recovery compared to aMSCs in wild type rat MI model. Mason trichrome staining with heart sections revealed that decreased fibrosis was evident on nMSCs injection compared to aMSCs in both athymic and wild type rat MI model. Myocardial sections from rats received nMSCs showed significantly reduced M1 macrophages (inflammatory) and increased M2 macrophages (anti-inflammatory) compared with sections from rats having received aMSCs and IMDM control. Pro and anti-inflammatory cytokines analyzed on sera collected on day 2 and 7 revealed that anti-inflammatory cytokine (IL10) was significantly increased and inflammatory cytokines (IL4 and IL12) reduced in nMSCs compared to aMSCs transplanted MI rat model.In conclusion, nMSCs demonstrated superior functional abilities, reduced fibrosis, inflammatory cells and cytokines compared to all the other cell types and with aMSCs demonstrating that nMSCs is an ideal stem cell type for therapeutic application in myocardial infarction.

scholarly journals BIRB 796 has Distinctive Anti-inflammatory Effects on Different Cell Types

2013 ◽  
Vol 13 (6) ◽  
pp. 283 ◽  
Author(s):  
Soyoon Ryoo ◽  
Jida Choi ◽  
Jaemyung Kim ◽  
Suyoung Bae ◽  
Jaewoo Hong ◽  
...  
Keyword(s):  
Cell Types ◽  
Anti Inflammatory ◽  
Different Cell Types

Abstract 16995: Anti-Inflammatory and Immuno-Modulatory Properties of Neonatal MSC

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sudhish Sharma ◽  
Rachana Mishra ◽  
Progyaparamita Saha ◽  
Muthukumar Gunasekaran ◽  
Aakash Shah ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Serum Levels ◽  
Cell Types ◽  
Treg Cells ◽  
Dependent Manner ◽  
Iri Model ◽  
Ifn Gamma ◽  
T Lymphocyte Proliferation ◽  
Adult Mesenchymal Stem Cells ◽  
Anti Inflammatory

Background: Anti-inflammatory and immunomodulatory properties are prerequisites for the success of cell therapy as shown by adult Mesenchymal Stem cells (MSC) by reducing both B- and T-lymphocyte proliferation, in a paracrine dependent manner. Proteomics of neonatal MSCs (nMSCs) has identified the superior quality of secretome containing a significantly higher number of anti-inflammatory (68 vs 21 in aMSCs) molecules. Hypothesis: nMSCs have potent anti-inflammatory and immunomodulatory characteristics as compared to other cell types currently being used as cell therapy. Methods: nMSC were tested and compared to other cell types for: a) Hypo-immunogenicity (expression of MHCII in the presence of IFN-gamma), b) immunogenicity (reduce proliferation of human CD4+ T-cells in a co-culture mixed lymphocyte reaction (MLR), c) anti-inflammatory properties (reduce IL-8 secretion of macrophages in the presence of Nigericin, d) systematic immune response (using rat myocardial infarction (MI) model (IL10, TNF-a and IL12)) and e) Immunomodulation (CD4+ cells to T reg CD4 + /CD25 + /FoxP3 + ). Results: Expression of MHCII on nMSCs, after 72 hours of exposure to IFN-gamma and proliferation of CD4 + cells in MLR was significantly (40±3.8% and 55±4.3%, n=5) reduced as compared to aMSC or CDC. IL8 was measured in the supernatants of nMSC derived secretome reduced the secretion of IL8 from activated macrophages in a dose dependent manner (150 ug protein/ml). Intravenous injection of nMSCs in a rat MI model significantly reduced serum levels of of TNF-α and IL-12 while upregulated IL-10 and improving myocardial function. While BM-MSCs and aMSCs failed to significantly modulate immune system, nMSC significantly increased the number of Treg cells as compared to CDC. Similar results were observed with Pig IRI model. Conclusions: Together, in a head-to-head comparison, nMSCs outperformed all other competitive cell types currently under investigation for their tissue repairing role, including CDCs and BM-MSCs to achieve the highest clinical efficacy.

TMOD-21. A NOVEL IN-VITRO METHOD TO MODEL MACROPHAGES IN GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi220-vi220
Author(s):  
Hasan Alrefai ◽  
Andee Beierle ◽  
Lauren Nassour ◽  
Nicholas Eustace ◽  
Zeel Patel ◽  
...  
Keyword(s):  
Cell Types ◽  
In Vitro Models ◽  
Tumor Initiating Cells ◽  
Serum Free ◽  
Brain Tumor Initiating Cells ◽  
Multiple Cell ◽  
Anti Inflammatory ◽  
Free Media ◽  
Inflammatory Macrophages

Abstract BACKGROUND The GBM tumor microenvironment (TME) is comprised of a plethora of cancerous and non-cancerous cells that contribute to GBM growth, invasion, and chemoresistance. In-vitro models of GBM typically fail to incorporate multiple cell types. Others have addressed this problem by employing 3D bioprinting to incorporate astrocytes and macrophages in an extracellular matrix; however, they used serum-containing media and classically polarized anti-inflammatory macrophages. Serum has been shown to cause GBM brain-tumor initiating cells to lose their stem-like properties, highlighting the importance of excluding it from these models. Additionally, tumor-associated macrophages (TAMs) do not adhere to the traditional M2 phenotype. METHODS THP-1 monocytes and normal human astrocytes (NHAs) were transitioned into serum-free HL-1 and neurobasal-based media, respectively. Monocytes were stimulated towards a macrophage-like state with PMA and polarized by co-culturing them with GBM patient-derived xenograft(PDX) lines, using a transwell insert. CD206 expression was used to validate polarization and a cytokine array was used to characterize the cells. RESULTS There was no difference in proliferation rates at 72 hours for THP-1 monocytes grown in serum-free HL-1 media compared to serum-containing RPMI 1640 (p > 0.95). Macrophages polarized via transwell inserts expressed the lymphocyte chemoattractant protein, CCL2, whereas resting(M0), pro-inflammatory(M1), and anti-inflammatory(M2) macrophages did not. Additionally, these macrophages expressed more CXCL1 and IL-1ß relative to M1 macrophages. We have also demonstrated a method to maintain a tri-culture model of GBM PDX cells, NHAs, and TAMs in a serum-free media that supports the growth/maintenance of all cell types. CONCLUSIONS We have demonstrated a novel method by which we can polarize macrophages towards a tumor-supportive phenotype that differs in cytokine expression from traditionally polarized macrophages. This higher-fidelity method of modeling TAMs in GBM can aid in the development of targeted therapeutics that may one day enter the clinic in hopes of improving outcomes in GBM.

Laser-assisted microdissection and real-time PCR detect anti-inflammatory effect of perfluorocarbon

2003 ◽  
Vol 285 (1) ◽  
pp. L55-L62 ◽  
Author(s):  
Katharina von der Hardt ◽  
Michael Andreas Kandler ◽  
Ludger Fink ◽  
Ellen Schoof ◽  
Jörg Dötsch ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mrna Expression ◽  
Vascular Smooth Muscle Cells ◽  
Alveolar Macrophages ◽  
Real Time Pcr ◽  
Muscle Cells ◽  
Cell Types ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The aim of this study was to identify cell types involved in the anti-inflammatory effect of ventilation with perfluorocarbon in vivo. Fifteen anesthetized, surfactant-depleted piglets received either aerosolized perfluorocarbon (Aerosol-PFC), partial liquid ventilation (rLV) at functional residual capacity (FRC) volume (FRC-PLV), or intermittent mandatory ventilation (control). After laser-assisted microdissection of different lung cell types, mRNA expression of IL-8 and ICAM-1 was determined using TaqMan real-time PCR normalized to hypoxanthine phosphoribosyltransferase (HPRT). IL-8 mRNA expression (means ± SE; control vs. Aerosol-PFC) was 356 ± 142 copies IL-8 mRNA/copy HPRT mRNA vs. 3.5 ± 1.8 in alveolar macrophages ( P <0.01); 208 ± 108 vs. 2.7 ± 0.8 in bronchiolar epithelial cells ( P <0.05); 26 ± 11 vs. 0.7 ± 0.2 in alveolar septum cells ( P <0.01); 2.8 ± 1.0 vs. 0.8 ± 0.4 in bronchiolar smooth muscle cells ( P <0.05); and 1.1 ± 0.4 vs. 0.2 ± 0.05 in vascular smooth muscle cells ( P <0.05). With FRC-PLV, IL-8/HPRT mRNA expression was significantly lower in macrophages, bronchiolar epithelial, and vascular smooth muscle cells. ICAM-1 mRNA expression in vascular endothelial cells remained unchanged. Predominantly, alveolar macrophages and bronchiolar epithelial cells were involved in the inflammatory pulmonary process. The anti-inflammatory effect of Aerosol-PFC was most pronounced.

scholarly journals Synthesis and Anticancer Activity of CDDO and CDDO-Me, Two Derivatives of Natural Triterpenoids

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4097 ◽  
Author(s):  
Rebecca Borella ◽  
Luca Forti ◽  
Lara Gibellini ◽  
Anna De Gaetano ◽  
Sara De Biasi ◽  
...  
Keyword(s):  
Biological Effects ◽  
Chemical Properties ◽  
Cell Types ◽  
Telomerase Activity ◽  
Culture Cell ◽  
Protease Inhibition ◽  
Mitochondrial Functions ◽  
Anti Inflammatory ◽  
Apoptotic Pathways ◽  
Derivatives Of

Triterpenoids are natural compounds synthesized by plants through cyclization of squalene, known for their weak anti-inflammatory activity. 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), and its C28 modified derivative, methyl-ester (CDDO-Me, also known as bardoxolone methyl), are two synthetic derivatives of oleanolic acid, synthesized more than 20 years ago, in an attempt to enhance the anti-inflammatory behavior of the natural compound. These molecules have been extensively investigated for their strong ability to exert antiproliferative, antiangiogenic, and antimetastatic activities, and to induce apoptosis and differentiation in cancer cells. Here, we discuss the chemical properties of natural triterpenoids, the pathways of synthesis and the biological effects of CDDO and its derivative CDDO-Me. At nanomolar doses, CDDO and CDDO-Me have been shown to protect cells and tissues from oxidative stress by increasing the transcriptional activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2). At doses higher than 100 nM, CDDO and CDDO-Me are able to modulate the differentiation of a variety of cell types, both tumor cell lines or primary culture cell, while at micromolar doses these compounds exert an anticancer effect in multiple manners; by inducing extrinsic or intrinsic apoptotic pathways, or autophagic cell death, by inhibiting telomerase activity, by disrupting mitochondrial functions through Lon protease inhibition, and by blocking the deubiquitylating enzyme USP7. CDDO-Me demonstrated its efficacy as anticancer drugs in different mouse models, and versus several types of cancer. Several clinical trials have been started in humans for evaluating CDDO-Me efficacy as anticancer and anti-inflammatory drug; despite promising results, significant increase in heart failure events represented an obstacle for the clinical use of CDDO-Me.

P151 DISRUPTION OF ENDOGENOUS ITACONATE PRODUCTION EXACERBATES EXPERIMENTAL COLITIS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S5-S6
Author(s):  
Ryan Frieler ◽  
Thomas Vigil ◽  
Richard Mortensen ◽  
Yatrik Shah
Keyword(s):  
Gene Expression ◽  
Immune Cell ◽  
Tricarboxylic Acid Cycle ◽  
Myeloid Cells ◽  
Experimental Colitis ◽  
Cell Types ◽  
Cell Phenotype ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Anti Inflammatory

Abstract Background Inflammation is a hallmark of inflammatory bowel disease and alterations in tricarboxylic acid cycle (TCA) metabolism have been identified as major regulators of immune cell phenotype during inflammation and hypoxia. The TCA cycle metabolite, itaconate, is produced by the enzyme aconitate decarboxylase 1 (Acod1) and is highly upregulated during classical macrophage activation and during experimental colitis. Itaconate and cell permeable derivatives have robust anti-inflammatory effects on macrophages, therefore we hypothesized that Acod1-produced itaconate has a protective, anti-inflammatory effect during experimental colitis. Methods and Results Wild type (WT) control and Acod1-/- mice were administered 3% Dextran Sulfate Sodium (DSS) in water for 7 days to induce experimental colitis. After DSS was discontinued, Acod1-/- mice had significantly reduced body weight recovery with increased macroscopic disease severity, and upon dissection had decreased colon length and more severe inflammation. To determine if myeloid cells are the critical Acod1/itaconate-producing cell types, we generated myeloid-specific Acod1 deficient mice, however no differences in weight loss, colon length or inflammatory gene expression were detected compared to WT controls. To test whether supplementation with exogenous itaconate could ameliorate colitis, WT mice were treated with the cell-permeable form of itaconate, dimethyl itaconate (DMI). Administration of DMI significantly improved recovery after 7 days of DSS treatment and significantly reduced inflammatory gene expression in the colon. Conclusion Our data suggest that Acod1-produced itaconate has an important role in the regulation of inflammation during experimental colitis. Although myeloid cells have been thought to be major producers of Acod1 and itaconate, our data indicate that other cell types are involved. These results highlight the importance of this immunometabolic pathway and suggest that preservation or enhancement of this pathway with natural metabolites or metabolite derivatives could have beneficial effects during colitis.

scholarly journals Identification of a Kavain Analog with Efficient Anti-inflammatory Effects

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Olivier Huck ◽  
Xiaxian Han ◽  
Hannah Mulhall ◽  
Iryna Gumenchuk ◽  
Bin Cai ◽  
...  
Keyword(s):  
Joint Destruction ◽  
Cell Types ◽  
Interferon Γ ◽  
Piper Methysticum ◽  
Tnf Α ◽  
Osteoclast Activation ◽  
Anti Inflammatory ◽  
Soft Tissue Inflammation

Abstract Kavain, a compound derived from Piper methysticum, has demonstrated anti-inflammatory properties. To optimize its drug properties, identification and development of new kavain-derived compounds was undertaken. A focused library of analogs was synthesized and their effects on Porphyromonas gingivalis (P. gingivalis) elicited inflammation were evaluated in vitro and in vivo. The library contained cyclohexenones (5,5-dimethyl substituted cyclohexenones) substituted with a benzoate derivative at the 3-position of the cyclohexanone. The most promising analog identifed was a methylated derivative of kavain, Kava-205Me (5,5-dimethyl-3-oxocyclohex-1-en-1-yl 4-methylbenzoate.) In an in vitro assay of anti-inflammatory effects, murine macrophages (BMM) and THP-1 cells were infected with P. gingivalis (MOI = 20:1) and a panel of cytokines were measured. Both cell types treated with Kava-205Me (10 to 200 μg/ml) showed significantly and dose-dependently reduced TNF-α secretion induced by P. gingivalis. In BMM, Kava-205Me also reduced secretion of other cytokines involved in the early phase of inflammation, including IL-12, eotaxin, RANTES, IL-10 and interferon-γ (p < 0.05). In vivo, in an acute model of P. gingivalis-induced calvarial destruction, administration of Kava-205Me significantly improved the rate of healing associated with reduced soft tissue inflammation and osteoclast activation. In an infective arthritis murine model induced by injection of collagen-antibody (ArthriomAb) + P. gingivalis, administration of Kava-205Me was able to reduce efficiently paw swelling and joint destruction. These results highlight the strong anti-inflammatory properties of Kava-205Me and strengthen the interest of testing such compounds in the management of P. gingivalis elicited inflammation, especially in the management of periodontitis.

scholarly journals Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells

2020 ◽  
Vol 21 (16) ◽  
pp. 5905
Author(s):  
Maria Camilla Ciardulli ◽  
Luigi Marino ◽  
Erwin Pavel Lamparelli ◽  
Maurizio Guida ◽  
Nicholas Robert Forsyth ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Types ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Differentiation Factor ◽  
Anti Inflammatory ◽  
Growth Differentiation Factor 5

Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to human Growth Differentiation Factor 5 (hGDF-5) we supplemented each at doses of 1, 10, and 100 ng/mL of hGDF-5 and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated the expression of collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis-A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed up-regulation of SCX-A (1.7-fold) at Day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX-A (3.8-fold) and TNC (2.3-fold) after three days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular-shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this, we explored the expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines up-regulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold), but a greater up-regulation of IL-10 (2.5-fold). Type 1 collagen and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification with a length/width ratio increase, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue-engineering protocols.

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