Molecular Mechanisms Responsible for Anti-inflammatory and Immunosuppressive Effects of Mesenchymal Stem Cell-Derived Factors

2018 ◽  
pp. 187-206 ◽  
Author(s):  
C. Randall Harrell ◽  
Marina Gazdic Jankovic ◽  
Crissy Fellabaum ◽  
Ana Volarevic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Molecular Mechanisms ◽  
Anti Inflammatory

The Molecular Mechanisms Through Which Placental Mesenchymal Stem Cell‐Derived Extracellular Vesicles Promote Myelin Regeneration

2022 ◽  
pp. 2101099
Author(s):  
Kaitlin C. Clark ◽  
David Wang ◽  
Priyadarsini Kumar ◽  
Sirjan Mor ◽  
Edwin Kulubya ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms

Mesenchymal Stem Cell Conditioned Medium as Good as Methyl Prednisolone in Decreasing Levels of Interleukin 10 and The Degree of Pulmonary Vasculitis in Lupus Mice

2021 ◽  
Vol 20 (2) ◽  
pp. 426-430
Author(s):  
Nurhasan Agung Prabowo ◽  
Zainal Arifin Adnan ◽  
Arief Nurudhin ◽  
Yulyani Werdiningsih ◽  
Kukuh Prasetyo
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Conditioned Medium ◽  
Interleukin 10 ◽  
Control Group ◽  
Standard Drug ◽  
Methyl Prednisolone ◽  
Pulmonary Vasculitis ◽  
Anti Inflammatory ◽  
Cell Conditioned Medium

Background: Systemic lupus erythematosus is a chronic autoimmune disease that affects target organs. mesenchymal stem cell conditioned medium has immunosuppressive, anti-inflammatory, and immunoregulatory properties in lupus. Methyl prednisolone is a standard drug for lupus with immunosuppressive and anti-inflammatory properties. This study aims to compare the therapeutic effect of mesenchymal stem cell conditioned medium administration compared to methyl prednisolone on interleukin 10 levels and the degree of pulmonary vasculitis of lupus mice. Methods: The subjects were 24 female mice of Mus musculus Balb/C strain, which were categorized into 4 groups of 8 mice, i.e. the control group receiving 0.5 cc of 0.9% NaCl injection and placebo, the lupus group receiving 0.5 cc of pristane injection and placebo, and the treatment mesenchymal stem cell conditioned medium group receiving 0.5 cc pristane injection and mesenchymal stem cell conditioned medium 0,5 cc, and methylprednisolone group receiving 0,5 cc pristiane injection and methylprednisolone p.o 1,5 mg/kgbodyweight. After 24 days the mice were terminated and kidney and blood samples were taken. Statistical analysis was performed using ANOVA test followed by independent T-test. The p value was considered significant when the p < 0.05. Results: The study showed that there was no difference on the levels of interleukin level10 among mesenchymal stem cell conditioned medium goup and methyl prednisolone group (CM = 5,94 ± 2,49 pg/mL, mp = 5,86+1,73 pg/mL; p = 1) and the degree of pulmonary vasculitis (CM= 1,94 ± 0,25, MP=1,89+ 0,11 pg/ml; p = 0.667). Mesenchymal stem cell conditioned medium as good as methyl prednisolone in decreasing levels of interleukin 10 and the degree of pulmonary vasculitis in lupus mice. Conclusion: Mesenchymal stem cell conditioned medium as good as methyl prednisolone in decreasing levels of interleukin 10 and the degree of pulmonary vasculitis in lupus mice Bangladesh Journal of Medical Science Vol.20(2) 2021 p.426-430

scholarly journals Multifactorial Experimental Design to Optimize the Anti-Inflammatory and Proangiogenic Potential of Mesenchymal Stem Cell Spheroids

Stem Cells ◽  
2017 ◽  
Vol 35 (6) ◽  
pp. 1493-1504 ◽  
Author(s):  
Kaitlin C. Murphy ◽  
Jacklyn Whitehead ◽  
Patrick C. Falahee ◽  
Dejie Zhou ◽  
Scott I. Simon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Experimental Design ◽  
Mesenchymal Stem Cell ◽  
Cell Spheroids ◽  
Anti Inflammatory

scholarly journals Mesenchymal stem cell therapy efficacy in COVID-19 patients: A systematic review and meta-analysis

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 956
Author(s):  
Andrianto Andrianto ◽  
Desak Ketut Sekar Cempaka Putri ◽  
Makhyan Jibril Al Farabi ◽  
Teuku Yusrizal ◽  
Hanestya Oky Hermawan
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Adverse Events ◽  
Inflammatory Cytokines ◽  
Meta Analysis ◽  
Group Versus ◽  
Mechanical Ventilators ◽  
Mesenchymal Stem Cell Therapy ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Objective: To evaluate mesenchymal stem cell (MSC) administration safety and efficacy in COVID-19 patients. Methods: We conducted a literature search on PubMed/MEDLINE, medRxiv, EBSCOhost/CINAHL, ProQuest, and Scopus with keywords adjusted to each search engine’s specifications on February 12, 2021. Interventional studies that reviewed MSC efficacy (mortality, hospitalization duration, need for mechanical ventilators, and inflammation markers) and/or safety (adverse events) in COVID-19 patients who were 18 years old or more were included in this study. Study eligibility, data extraction, and study quality assessment were conducted independently by each author. Results: A total of five studies of moderate to high quality with a total of 193 patients were included. One of the three randomized studies included did not apply blinding to either participants or medical professionals. Pooled OR (Odd Ratio) for mortality risk, adverse events incidence, and use of mechanical ventilators for patients on MSC therapy were 0.13 [95% CI: 0.02, 0.68], 0.91 [95% CI: 0.45, 1.86], and 0.42 [95% CI: 0.12, 1.47], respectively. Pooled mean difference for hospitalization duration in the MSC group versus the control was -3.54 [CI 95%: -4.68, -2.40] with 7% heterogeneity. All studies agreed that there was an increase of pro-inflammatory cytokines and a decrease of anti-inflammatory markers that were statistically different in the MSC group. Conclusion: Mesenchymal stem cell administration to COVID-19 patients is safe and effective in reducing mortality and hospitalization duration. Furthermore, a decrease of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines were observed.

scholarly journals Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1605 ◽  
Author(s):  
Carl Randall Harrell ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
Nebojsa Arsenijevic ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Experimental Studies ◽  
Bioactive Molecules ◽  
Therapeutic Effects

There is growing evidence that mesenchymal stem cell (MSC)-based immunosuppression was mainly attributed to the effects of MSC-derived extracellular vesicles (MSC-EVs). MSC-EVs are enriched with MSC-sourced bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs), cytokines, chemokines, immunomodulatory factors) that regulate phenotype, function and homing of immune cells. In this review article we emphasized current knowledge regarding molecular mechanisms responsible for the therapeutic effects of MSC-EVs in attenuation of autoimmune and inflammatory diseases. We described the disease-specific cellular targets of MSC-EVs and defined MSC-sourced molecules, which were responsible for MSC-EV-based immunosuppression. Results obtained in a large number of experimental studies revealed that both local and systemic administration of MSC-EVs efficiently suppressed detrimental immune response in inflamed tissues and promoted survival and regeneration of injured parenchymal cells. MSC-EVs-based anti-inflammatory effects were relied on the delivery of immunoregulatory miRNAs and immunomodulatory proteins in inflammatory immune cells (M1 macrophages, dendritic cells (DCs), CD4+Th1 and Th17 cells), enabling their phenotypic conversion into immunosuppressive M2 macrophages, tolerogenic DCs and T regulatory cells. Additionally, through the delivery of mRNAs and miRNAs, MSC-EVs activated autophagy and/or inhibited apoptosis, necrosis and oxidative stress in injured hepatocytes, neurons, retinal cells, lung, gut and renal epithelial cells, promoting their survival and regeneration.

scholarly journals PDGF-BB and IL-4 co-overexpression is a potential strategy to enhance mesenchymal stem cell-based bone regeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ning Zhang ◽  
Chi-Wen Lo ◽  
Takeshi Utsunomiya ◽  
Masahiro Maruyama ◽  
Ejun Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Chronic Inflammation ◽  
Lentiviral Vector ◽  
Great Promise ◽  
Anti Inflammatory ◽  
Potential Strategy

Abstract Background Mesenchymal stem cell (MSC)-based therapy has the potential for immunomodulation and enhancement of tissue regeneration. Genetically modified MSCs that over-express specific cytokines, growth factors, or chemokines have shown great promise in pre-clinical studies. In this regard, the anti-inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory M2 phenotype; M2 macrophages mitigate chronic inflammation and enhance osteogenesis by MSC lineage cells. However, exposure to IL-4 prematurely inhibits osteogenesis of MSCs in vitro; furthermore, IL-4 overexpressing MSCs inhibit osteogenesis in vivo during the acute inflammatory period. Platelet-derived growth factor (PDGF)-BB has been shown to enhance osteogenesis of MSCs with a dose-dependent effect. Methods In this study, we generated a lentiviral vector that produces PDGF-BB under a weak promoter (phosphoglycerate kinase, PGK) and lentiviral vector producing IL-4 under a strong promoter (cytomegalovirus, CMV). We infected MSCs with PDGF-BB and IL-4-producing lentiviral vectors separately or in combination to investigate cell proliferation and viability, protein expression, and the capability for osteogenesis. Results PDGF-BB and IL-4 co-overexpression was observed in the co-infected MSCs and shown to enhance cell proliferation and viability, and osteogenesis compared to IL-4 overexpressing MSCs alone. Conclusions Overexpression of PDGF-BB together with IL-4 mitigates the inhibitory effect of IL-4 on osteogenesis by IL-4 overexpressing MSCS. PDGF-BB and IL-4 overexpressing MSCs may be a potential strategy to facilitate osteogenesis in scenarios of both acute and chronic inflammation.

Mesenchymal Stem Cell Anti-Microbial and Anti-Inflammatory Therapeutic Optimization Through Effector Manipulation

2019 ◽  
Author(s):  
T.L. Bonfield ◽  
M.T. Sutton ◽  
M. Majumder ◽  
J. Jensen ◽  
M. Folz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Anti Inflammatory

scholarly journals Mesenchymal Stem Cell Derived Biocompatible Membrane Vesicles Demonstrate Immunomodulatory Activity Inhibiting Activation and Proliferation of Human Mononuclear Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 577
Author(s):  
Marina Gomzikova ◽  
Sevindzh Kletukhina ◽  
Sirina Kurbangaleeva ◽  
Olga Neustroeva ◽  
Olga Vasileva ◽  
...  
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
B Cells ◽  
T Lymphocytes ◽  
Mesenchymal Stem Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Membrane Vesicles ◽  
Immunomodulatory Activity ◽  
Anti Inflammatory

Immune-mediated diseases are characterized by abnormal activity of the immune system. The cytochalasin B-induced membrane vesicles (CIMVs) are innovative therapeutic instruments. However, the immunomodulating activity of human mesenchymal stem cell (MSC)-derived CIMVs (CIMVs-MSCs) remains unknown. Therefore, we sought to investigate the immunological properties of CIMVs-MSCs and evaluate their effect on human peripheral blood mononuclear cells (PBMCs). We found that CIMVs-MSCs are primarily uptaken by monocytes and B-cells. Additionally, we demonstrated that CIMVs-MSCs inhibit phytohemagglutinin (PHA)-induced proliferation of PBMCs, with more pronounced effect on T-lymphocytes expansion as compared to that of B-cells. In addition, activation of T-helpers (CD4+CD25+), B-cells (CD19+CD25+), and T-cytotoxic lymphocytes (CD8+CD25+) was also significantly suppressed by CIMVs-MSCs. Additionally, CIMVs-MSCs decreased secretion of epidermal growth factor (EGF) and pro-inflammatory Fractalkine in a population of PBMCs, while the releases of FGF-2, G-CSF, anti-inflammatory GM-CSF, MCP-3, anti-inflammatory MDC, anti-inflammatory IL-12p70, pro-inflammatory IL-1b, and MCP-1 were increased. We analyzed the effect of CIMVs-MSCs on an isolated population of CD4+ and CD8+ T-lymphocytes and demonstrated their different immune response and cytokine secretion. Finally, we observed that no xenogeneic nor allogeneic transplantation of CIMVs induced an immune response in mice. Our data suggest that CIMVs-MSCs have immunosuppressive properties, are potential agents for immunomodulating treatment, and are worthy of further investigation.

scholarly journals Intravenous administration of anti-inflammatory mesenchymal stem cell spheroids reduces chronic alcohol intake and abolishes binge-drinking

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Fernando Ezquer ◽  
Paola Morales ◽  
María Elena Quintanilla ◽  
Daniela Santapau ◽  
Carolyne Lespay-Rebolledo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Binge Drinking ◽  
Intravenous Administration ◽  
Alcohol Intake ◽  
Chronic Alcohol ◽  
Cell Spheroids ◽  
Anti Inflammatory
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