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Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate

Vibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and s...

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Published in:Stem cell research & therapy 2021-11, Vol.12 (1), p.564-564, Article 564
Main Authors: Bahroudi, Mahboube, Bakhshi, Bita, Soudi, Sara, Najar-Peerayeh, Shahin
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description Vibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and septic shock. Mesenchymal stem cells (MSCs) are currently used to treat infectious and inflammatory diseases. Therefore, this study aimed to evaluate the immune-modulating effects of the LPS-MSC-conditioned medium (CM) on V. cholerae LPS immunization in a murine model. After preconditioning MSCs with LPS, mice were immunized intraperitoneally on days 0 and 14 with the following combinations: LPS + LPS-MSC-CM; detoxified LPS (DLPS) + MSC-CM; LPS + MSC sup; LPS; LPS-MSC-CM; MSC supernatant (MSC sup); and PBS. The mouse serum and saliva samples were collected to evaluate antibody (serum IgG and saliva IgA) and cytokine responses (TNF-α, IL-10, IL-6, TGF-β, IL-4, IL-5, and B-cell activating factor (BAFF)). The LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P 
doi_str_mv 10.1186/s13287-021-02622-0
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Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and septic shock. Mesenchymal stem cells (MSCs) are currently used to treat infectious and inflammatory diseases. Therefore, this study aimed to evaluate the immune-modulating effects of the LPS-MSC-conditioned medium (CM) on V. cholerae LPS immunization in a murine model. After preconditioning MSCs with LPS, mice were immunized intraperitoneally on days 0 and 14 with the following combinations: LPS + LPS-MSC-CM; detoxified LPS (DLPS) + MSC-CM; LPS + MSC sup; LPS; LPS-MSC-CM; MSC supernatant (MSC sup); and PBS. The mouse serum and saliva samples were collected to evaluate antibody (serum IgG and saliva IgA) and cytokine responses (TNF-α, IL-10, IL-6, TGF-β, IL-4, IL-5, and B-cell activating factor (BAFF)). The LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P &lt; 0.001). TNF-α levels, in contrast to IL-10 and TGF-β, were reduced significantly in mice receiving the LPS + LPS-MSC-CM compared to mice receiving only LPS. IL-4, IL-5, and BAFF levels significantly increased in mice receiving increased doses of LPS + LPS-MSC-CM compared to those who received only LPS. The highest vibriocidal antibody titer (1:64) was observed in LPS + LPS-MSC-CM-immunized mice and resulted in a significant improvement in survival in infant mice infected by V. cholerae O1. The LPS-MSC-CM modulates the immune response to V. cholerae LPS by regulating inflammatory and anti-inflammatory responses and inducing vibriocidal antibodies, which protect neonate mice against V. cholerae infection.</description><identifier>ISSN: 1757-6512</identifier><identifier>EISSN: 1757-6512</identifier><identifier>DOI: 10.1186/s13287-021-02622-0</identifier><identifier>PMID: 34732259</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Animal models ; Animals ; Antibodies ; Antibodies, Bacterial ; Antibody ; Antigens ; Antimicrobial agents ; BLyS protein ; Cholera ; Cholera toxin ; Culture Media, Conditioned - pharmacology ; Cytokine ; Cytokines ; Cytotoxicity ; Drug dosages ; Drug resistance ; Flow cytometry ; Humans ; Immune response ; Immunity ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Immunomodulation ; Inflammation ; Inflammatory diseases ; Interleukin 10 ; Interleukin 4 ; Interleukin 5 ; Interleukin 6 ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; LPS ; Lymphocytes B ; Medical research ; Medicine, Experimental ; Mesenchymal Stem Cells ; Mice ; Mitogens ; Morbidity ; Saliva ; Septic shock ; Stem cell transplantation ; Stem cells ; Transforming growth factors ; Tumor necrosis factor-α ; Vaccines ; Vibrio cholerae ; Vibrio cholerae O1</subject><ispartof>Stem cell research &amp; therapy, 2021-11, Vol.12 (1), p.564-564, Article 564</ispartof><rights>2021. 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therapy</jtitle><addtitle>Stem Cell Res Ther</addtitle><date>2021-11-03</date><risdate>2021</risdate><volume>12</volume><issue>1</issue><spage>564</spage><epage>564</epage><pages>564-564</pages><artnum>564</artnum><issn>1757-6512</issn><eissn>1757-6512</eissn><abstract>Vibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and septic shock. Mesenchymal stem cells (MSCs) are currently used to treat infectious and inflammatory diseases. Therefore, this study aimed to evaluate the immune-modulating effects of the LPS-MSC-conditioned medium (CM) on V. cholerae LPS immunization in a murine model. After preconditioning MSCs with LPS, mice were immunized intraperitoneally on days 0 and 14 with the following combinations: LPS + LPS-MSC-CM; detoxified LPS (DLPS) + MSC-CM; LPS + MSC sup; LPS; LPS-MSC-CM; MSC supernatant (MSC sup); and PBS. The mouse serum and saliva samples were collected to evaluate antibody (serum IgG and saliva IgA) and cytokine responses (TNF-α, IL-10, IL-6, TGF-β, IL-4, IL-5, and B-cell activating factor (BAFF)). The LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P &lt; 0.001). 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subjects Analysis
Animal models
Animals
Antibodies
Antibodies, Bacterial
Antibody
Antigens
Antimicrobial agents
BLyS protein
Cholera
Cholera toxin
Culture Media, Conditioned - pharmacology
Cytokine
Cytokines
Cytotoxicity
Drug dosages
Drug resistance
Flow cytometry
Humans
Immune response
Immunity
Immunization
Immunoglobulin A
Immunoglobulin G
Immunomodulation
Inflammation
Inflammatory diseases
Interleukin 10
Interleukin 4
Interleukin 5
Interleukin 6
Lipopolysaccharides
Lipopolysaccharides - pharmacology
LPS
Lymphocytes B
Medical research
Medicine, Experimental
Mesenchymal Stem Cells
Mice
Mitogens
Morbidity
Saliva
Septic shock
Stem cell transplantation
Stem cells
Transforming growth factors
Tumor necrosis factor-α
Vaccines
Vibrio cholerae
Vibrio cholerae O1
title Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate
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