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

BACKGROUND: 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. METHODS: 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-ß, IL-4, IL-5, and B-cell activating factor (BAFF)). RESULTS: The LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P < 0.001). TNF-α levels, in contrast to IL-10 and TGF-ß, 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. CONCLUSIONS: 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.

Antibacterial and antibiofilm activity of bone marrow-derived human mesenchymal stem cells secretome against Vibrio cholerae.

The ability of V. cholerae to survive and spread in the aquatic environment combined with the scarcity of effective antimicrobial agents, especially those effective against multidrug-resistant strains highlights the need for alternative non-antibiotic approaches for the treatment of V. cholerae infections. The aim of this study was to specifically examine the potential direct effect of unstimulated MSC secretome on V. cholerae killing and biofilm formation as a representative of non-invasive enteric bacterial pathogen. The bmMSCs were characterized by the presence of CD44 and CD73 and the absence of CD45 and CD34 molecular markers. Moreover, self-regeneration and differentiation capacity of MSCs into adipocytes and osteogenic lineages was assessed by immunohistology (IHC) method. The antibacterial activity of unstimulated MSCs supernatant against V. cholerae in broth microdilution assay decreased the bacterial suspension from 108 CFU/ml to 107 CFU/ml and showed a significant antimicrobial activity in a dose-dependent manner at dilutions of 1:8 to 1:128 (P < 0.05). The role of MSC secretome without preconditioning in the prevention of biofilm formation was assessed through plate-crystal violet assay and showed high antibiofilm activity against V. cholerae also in dose-dependent manner. As antibacterial mechanisms of MSC secretome are different from conventional antibiotics, together with its antibiofilm activity, proposes its application as a novel therapeutic approach combatting multi-drug resistant pathogens with no fear of developing antimicrobial resistance.

Prevalence of cytotoxin-associated genes of Helicobacter pylori among Iranian GERD patients.

AIM: Since the impact of H. pylori and its virulence is not clear in GERD, this study aimed to evaluate the prevalence of cag A and cag E gens of H. pylori among Iranian GERD patients. BACKGROUND: Gastroesophageal reflux disease (GERD) is defined as a condition of reflux the stomach juice by low pH causes tissue damage. Helicobacter pylori may or may not influence the GERD; however, it is unclear. METHODS: This study was a case-control study performed on patients with GERD who underwent upper gastrointestinal endoscopy at Taleghani Hospital of Tehran, Iran. Prevalence of H. pylori and presence of the cag A and cag E genes in GERD and control group was investigated. RESULTS: H. pylori was detected in 54% and 62% of GERD and control groups respectively. Prevalence of cag A gene among GERD patients was 44.4% whereas among the control group it was 87%. Prevalence of the cag E among GERD patients and control group was 44.4% and 64% respectively. Coexistence of cag A and cag E in GERD patients was 25.7% and in the control patients it was 54.8%. CONCLUSION: We did not find correlation between H. pylori existence in GERD patients in comparison to the control group. Similar to other Asian studies, the presence of the cag A in control group was more than GERD patients significantly. The co-existence of cag A and cag E was also more in control group significantly.