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Title:
Mesenchymal stromal cells are more effective than the MSC secretome in diminishing injury and enhancing recovery following ventilator-induced lung injury | Intensive Care Medicine Experimental
Description:
Background The potential for mesenchymal stem cells (MSCs) to reduce the severity of experimental lung injury has been established in several pre-clinical studies. We have recently demonstrated that MSCs, and MSC-secreted factors (secretome), enhance lung repair and regeneration at 48 h following ventilation-induced lung injury (VILI). We wished to determine the potential for MSC therapy to exert beneficial effects in the early recovery phase following VILI when ongoing injury coexists with processes of repair, and to compare the efficacy of MSC therapy to the use of the secretome alone. Methods Male SpragueâDawley rats were anesthetized, oro-tracheally intubated, and subjected to high stretch mechanical ventilation until lung compliance had declined by 50 % of baseline. Animals were then weaned from mechanical ventilation, and anesthesia discontinued. Once awake and spontaneously ventilating, animals received an intravenous injection of either rodent MSCs (10 million/kg), MSC-conditioned medium, fibroblasts (10 million/kg), or vehicle. Thereafter, the animals were allowed to recover and the extent of lung injury/repair was determined after 4 h. Results Treatment with MSCs diminished injury and enhanced recovery following VILI to a greater extent compared to MSC-conditioned medium, with fibroblasts proving ineffective. MSCs, but not their conditioned medium, attenuated indices of lung injury including oxygenation, respiratory compliance, and lung edema. Total lung water as assessed by wet:dry ratio, bronchoalveolar lavage total inflammatory cell, neutrophil counts, and alveolar IL-6 concentrations were reduced in the animals that received MSC therapy. Conclusions The immunomodulating and/or reparative effect of MSCs is evident early after VILI in this model. MSC-conditioned medium was not as effective as the cells themselves in diminishing injury and restoring lung structure and function.
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lung, injury, msc, pubmed, cells, mscs, article, google, scholar, vili, mesenchymal, stem, therapy, medium, cas, effects, cell, repair, alveolar, recovery, animals, group, vehicle, fig, early, central, secretome, laffey, acute, research, msccm, ventilatorinduced, ventilation, treatment, effect, ireland, human, med, care, studies, compliance, conditioned, respiratory, curley, potential, beneficial, anesthesia, therapeutic, rat, data,
Topics {âď¸}
bone-marrow-derived stromal cells mesenchymal stem/stromal cells adult spragueâdawley rats male spragueâdawley rats f-12/mem-Îą medium supplemented article download pdf pro-inflammatory cytokines il-1β ventilator-induced lung injury mesenchymal stromal cells ventilation-induced lung injury mechanical stretch-induced injury msc-cm msc-conditioned medium mesenchymal stem cells alveolar fluid clearance intra-arterial blood pressure intraperitoneal ketamine 80 mg kgâ1 acute lung injury experimental lung injury mcauley df sustained hypercapnic acidosis tidal volume 6 ml kgâ1 phosphate buffered saline anti-inflammatory cytokine il-10 lung injury induced total lung water decreased lung oedema inflammatory cell infiltration experimental bronchopulmonary dysplasia msc-treated group versus full access enhancing bacterial clearance high stretch ventilation enhances injury resolution static lung compliance privacy choices/manage cookies bone marrow msc-treated animals compared t-cell proliferation [34] european research council keenan research centre bal bronchoalveolar lavage human lungs rejected alveolar il-6 concentrations alveolar il-10 concentrations received msc therapy msc therapy modulated hypercapnic acidosis article hayes quantitative stereological techniques versus partial restoration
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headline:Mesenchymal stromal cells are more effective than the MSC secretome in diminishing injury and enhancing recovery following ventilator-induced lung injury
description:The potential for mesenchymal stem cells (MSCs) to reduce the severity of experimental lung injury has been established in several pre-clinical studies. We have recently demonstrated that MSCs, and MSC-secreted factors (secretome), enhance lung repair and regeneration at 48Â h following ventilation-induced lung injury (VILI). We wished to determine the potential for MSC therapy to exert beneficial effects in the early recovery phase following VILI when ongoing injury coexists with processes of repair, and to compare the efficacy of MSC therapy to the use of the secretome alone. Male SpragueâDawley rats were anesthetized, oro-tracheally intubated, and subjected to high stretch mechanical ventilation until lung compliance had declined by 50Â % of baseline. Animals were then weaned from mechanical ventilation, and anesthesia discontinued. Once awake and spontaneously ventilating, animals received an intravenous injection of either rodent MSCs (10 million/kg), MSC-conditioned medium, fibroblasts (10 million/kg), or vehicle. Thereafter, the animals were allowed to recover and the extent of lung injury/repair was determined after 4Â h. Treatment with MSCs diminished injury and enhanced recovery following VILI to a greater extent compared to MSC-conditioned medium, with fibroblasts proving ineffective. MSCs, but not their conditioned medium, attenuated indices of lung injury including oxygenation, respiratory compliance, and lung edema. Total lung water as assessed by wet:dry ratio, bronchoalveolar lavage total inflammatory cell, neutrophil counts, and alveolar IL-6 concentrations were reduced in the animals that received MSC therapy. The immunomodulating and/or reparative effect of MSCs is evident early after VILI in this model. MSC-conditioned medium was not as effective as the cells themselves in diminishing injury and restoring lung structure and function.
datePublished:2015-10-15T00:00:00Z
dateModified:2015-10-15T00:00:00Z
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Acute respiratory distress syndrome
Inflammation
Ventilation-induced lung injury
Repair
Mesenchymal stem/stromal cell
Intensive / Critical Care Medicine
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headline:Mesenchymal stromal cells are more effective than the MSC secretome in diminishing injury and enhancing recovery following ventilator-induced lung injury
description:The potential for mesenchymal stem cells (MSCs) to reduce the severity of experimental lung injury has been established in several pre-clinical studies. We have recently demonstrated that MSCs, and MSC-secreted factors (secretome), enhance lung repair and regeneration at 48Â h following ventilation-induced lung injury (VILI). We wished to determine the potential for MSC therapy to exert beneficial effects in the early recovery phase following VILI when ongoing injury coexists with processes of repair, and to compare the efficacy of MSC therapy to the use of the secretome alone. Male SpragueâDawley rats were anesthetized, oro-tracheally intubated, and subjected to high stretch mechanical ventilation until lung compliance had declined by 50Â % of baseline. Animals were then weaned from mechanical ventilation, and anesthesia discontinued. Once awake and spontaneously ventilating, animals received an intravenous injection of either rodent MSCs (10 million/kg), MSC-conditioned medium, fibroblasts (10 million/kg), or vehicle. Thereafter, the animals were allowed to recover and the extent of lung injury/repair was determined after 4Â h. Treatment with MSCs diminished injury and enhanced recovery following VILI to a greater extent compared to MSC-conditioned medium, with fibroblasts proving ineffective. MSCs, but not their conditioned medium, attenuated indices of lung injury including oxygenation, respiratory compliance, and lung edema. Total lung water as assessed by wet:dry ratio, bronchoalveolar lavage total inflammatory cell, neutrophil counts, and alveolar IL-6 concentrations were reduced in the animals that received MSC therapy. The immunomodulating and/or reparative effect of MSCs is evident early after VILI in this model. MSC-conditioned medium was not as effective as the cells themselves in diminishing injury and restoring lung structure and function.
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Acute respiratory distress syndrome
Inflammation
Ventilation-induced lung injury
Repair
Mesenchymal stem/stromal cell
Intensive / Critical Care Medicine
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