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Cell Therapy Using Genetically Modified Mesenchymal Stem Cell in a Murine Model of Sepsis
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A1841 - Cell Therapy Using Genetically Modified Mesenchymal Stem Cell in a Murine Model of Sepsis
Author Block: J. Bringue; CIBER Enfermedades Respiratorias, Sabadell, Spain.
Background: Sepsis is an extreme inflammatory response mediated by cytokines that can induce acute lung injury and multi-organic dysfunction. Sepsis remains one of the leading causes of mortality in the intensive care units and there is not a specific treatment for this disease. Nowadays, we have to focus in new therapeutic strategies. Mesenchymal stem cells (MSC) have shown anti-inflammatory, antimicrobial, anti-apoptotic and regulatory properties, MSC could be an interesting therapy for sepsis however with the new molecular technic of genetically modification the beneficial effects of MSC therapy could be enhanced. Hypothesis: Treatment genetically modified MSC reduces the damage in a murine model of sepsis, modulating the inflammatory systemic response and diminishing the lung injury. Material and Methods: Sepsis was induced by a cecal ligation and puncture (CLP) in Sprague-Dawley rats (225-300 g). 6 hours later we did a surgical source control and administered antibiotics (Meropenem 20 mg/kg), fluids (10 ml/kg) and analgesics (Buprenorphine 0.025 mg / Kg). In addition, we administered 2.5*106 MSC genetically modified to overexpress Interleukin 10 and 7. 48 h later the animals were sacrificed and samples of lung tissue, bronchoalveolar lavage and blood were collected. We did control groups, rats were submitted to the same process but no CLP was performed. We analysed neutrophils, macrophages and lymphocytes in bronchoalveolar lavage; blood and spleen bacterial counts and expression of inflammatory cytokines in lung tissue. Results: Modified MSC compared to control MSC reduced number of neutrophils and proteins infiltrated into the alveolar space. Modified MSC also reduced the number of circulating bacteria in blood. In addition, modified MSC significantly reduced the expression of TNFα, iNOS, IL1β and CCL2 in lung tissue in the septic animals. Further analysis will be performed. Conclusion: Genetically modified MSC modulates the proinflammatory cytokine production during sepsis and increase the bacterial clearance in a murine model of sepsis
Author Block: J. Bringue; CIBER Enfermedades Respiratorias, Sabadell, Spain.
Background: Sepsis is an extreme inflammatory response mediated by cytokines that can induce acute lung injury and multi-organic dysfunction. Sepsis remains one of the leading causes of mortality in the intensive care units and there is not a specific treatment for this disease. Nowadays, we have to focus in new therapeutic strategies. Mesenchymal stem cells (MSC) have shown anti-inflammatory, antimicrobial, anti-apoptotic and regulatory properties, MSC could be an interesting therapy for sepsis however with the new molecular technic of genetically modification the beneficial effects of MSC therapy could be enhanced. Hypothesis: Treatment genetically modified MSC reduces the damage in a murine model of sepsis, modulating the inflammatory systemic response and diminishing the lung injury. Material and Methods: Sepsis was induced by a cecal ligation and puncture (CLP) in Sprague-Dawley rats (225-300 g). 6 hours later we did a surgical source control and administered antibiotics (Meropenem 20 mg/kg), fluids (10 ml/kg) and analgesics (Buprenorphine 0.025 mg / Kg). In addition, we administered 2.5*106 MSC genetically modified to overexpress Interleukin 10 and 7. 48 h later the animals were sacrificed and samples of lung tissue, bronchoalveolar lavage and blood were collected. We did control groups, rats were submitted to the same process but no CLP was performed. We analysed neutrophils, macrophages and lymphocytes in bronchoalveolar lavage; blood and spleen bacterial counts and expression of inflammatory cytokines in lung tissue. Results: Modified MSC compared to control MSC reduced number of neutrophils and proteins infiltrated into the alveolar space. Modified MSC also reduced the number of circulating bacteria in blood. In addition, modified MSC significantly reduced the expression of TNFα, iNOS, IL1β and CCL2 in lung tissue in the septic animals. Further analysis will be performed. Conclusion: Genetically modified MSC modulates the proinflammatory cytokine production during sepsis and increase the bacterial clearance in a murine model of sepsis
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