Mesenchymal Stem Cell: Does it Work in an Experimental Model with Acute Respiratory Distress Syndrome?

Yılmaz, Sema; Yıldızdaş, Dinçer; Subaşı, Cansu; Acikalin, Arbil; Kuyucu, Yurdun; Bayram, İbrahim; Topak, Ali; Tanyeli, Atila; Duruksu, Gökhan; Karaöz, Erdal

doi:10.1007/s12015-012-9395-2

Cited by 13 publications

(21 citation statements)

References 38 publications

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“…Increased BAL IL-1Ra has been shown in patients with ARDS, and is proposed as a potential endogenous antiinflammatory mediator to limit damage in acute lung injury (ALI) (37). Mesenchymal stem cells, which reduce lung injury in animal models, are associated with increased pulmonary IL-1Ra concentrations (38), whereas aerosolized Anankinra, recombinant human IL-1Ra, reduced pulmonary arterial pressure and gene expression of IL-8 and IL-1b in a porcine model of lung injury, suggesting a reparative role for exogenous IL-1Ra (39). Finally, exogenous IL-1Ra reduced pulmonary edema and protein permeability in a rodent model of ventilator-induced lung injury (40).…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte Growth Factor Promotes Epithelial Survival and Resolution in a Human Model of Lung Injury

Shyamsundar

McAuley

Ingram

et al. 2014

Am J Respir Crit Care Med

104

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Rationale: Increasing epithelial repair and regeneration may hasten resolution of lung injury in patients with the acute respiratory distress syndrome (ARDS). In animal models of ARDS, keratinocyte growth factor (KGF) reduces injury and increases epithelial proliferation and repair. The effect of KGF in the human alveolus is unknown.Objectives: To test whether KGF can attenuate alveolar injury in a human model of ARDS.Methods: Volunteers were randomized to intravenous KGF (60 mg/kg) or placebo for 3 days, before inhaling 50 mg LPS. Six hours later, subjects underwent bronchoalveolar lavage (BAL) to quantify markers of alveolar inflammation and cell-specific injury.Measurements and Main Results: KGF did not alter leukocyte infiltration or markers of permeability in response to LPS. KGF increased BAL concentrations of surfactant protein D, matrix metalloproteinase (MMP)-9, IL-1Ra, granulocyte-macrophage colony-stimulating factor (GM-CSF), and C-reactive protein.In vitro, BAL fluid from KGF-treated subjects inhibited pulmonary fibroblast proliferation, but increased alveolar epithelial proliferation. Active MMP-9 increased alveolar epithelial wound repair. Finally, BAL from the KGF-pretreated group enhanced macrophage phagocytic uptake of apoptotic epithelial cells and bacteria compared with BAL from the placebo-treated group. This effect was blocked by inhibiting activation of the GM-CSF receptor.Conclusions: KGF treatment increases BAL surfactant protein D, a marker of type II alveolar epithelial cell proliferation in a human model of acute lung injury. Additionally, KGF increases alveolar concentrations of the antiinflammatory cytokine IL-1Ra, and mediators that drive epithelial repair (MMP-9) and enhance macrophage clearance of dead cells and bacteria (GM-CSF). Clinical trial registered with ISRCTN 98813895.

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Section: Discussionmentioning

confidence: 99%

Keratinocyte Growth Factor Promotes Epithelial Survival and Resolution in a Human Model of Lung Injury

Shyamsundar

McAuley

Ingram

et al. 2014

Am J Respir Crit Care Med

104

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“…The mechanisms by which adult stem cells participate in the repair of the lung following injury have been attributed to their different qualities [16,25,52,53]. The ability of the cells to secrete paracrine factors, such as growth factors and anti-inflammatory cytokines, and to control oxidative damage, protect the endothelium and epithelium, transfer functional mitochondria and secrete antimicrobial peptides has been demonstrated to explain some of the therapeutic effects in the treatment of lung injury in animal in vivo and ex vivo models.…”

Section: Discussionmentioning

confidence: 99%

Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep

et al. 2014

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IntroductionAcute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill subjects, sepsis and severe bacterial pneumonia being its most common causes. The only interventions that have proven beneficial are protective ventilation strategies and fluid conservation approaches. New therapies are needed to address this common clinical problem. Others and we have previously shown the beneficial effect of infusion of exogenous adult stem cells in different pre-clinical models of ARDS.MethodsIn the present study endotoxin was infused intravenously into 14 sheep from which 6 received different doses of adult stem cells by intrabronchial delivery to evaluate the effect of stem cell therapy.ResultsAfter administration of endotoxin, there was a rapid decline in oxygenation to hypoxemic values, indicative of severe-to-moderate ARDS. None of the animals treated with saline solution recovered to normal baseline values during the 6 hours that the animals were followed. In contrast, sheep treated with a dose of 40 million adult stem cells returned their levels of oxygen in their blood to baseline two hours after the cells were infused. Similarly, improvements in carbon dioxide (CO2) clearance, pulmonary vascular pressures and inflammation were observed and confirmed by histology and by the decrease in lung edema.ConclusionsWe concluded that instillation of adult non-hematopoietic stem cells can diminish the impact of endotoxin and accelerate recovery of oxygenation, CO2 removal and inflammation in the ovine model, making the use of adult stem cells a real alternative for future therapies for ARDS.

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“…[10][11][12] In addition, MSC transplant causes decreased fibrosis in the heart, lung, liver, and kidney in experimental animal models. 8,[13][14][15][16] These results suggest that the beneficial effect is attributable to a reduction in the rejection by MSCs.…”

Section: Introductionmentioning

confidence: 78%

“…16,17 The femurs and tibias were excised, and the bone cavity was flushed with a standard culture medium using a 21-gauge needle. The marrow plug was suspended in a solution of phosphate-buffered saline (PBS) and separation medium (Histopaque, 1.077 g/mL, Sigma, St. Louis, MO, USA) and was centrifuged at 200 ×g for 10 minutes.…”

Section: Isolation and Culture Of Bone Marrow Mesenchymal Stem Cellsmentioning

confidence: 99%

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Özbek

Adaş²,

Ötünçtemur³

et al. 2015

Exp Clin Transplant

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Objectives: Mesenchymal stem cells hold promise for renal disease treatment. Vascular endothelial growth factor may heal tubule-interstitial fibrosis in unilateral ureteral obstruction by inhibiting epithelial-mesenchymal transition. We investigated the protective effect of vascular endothelial growth factor in transfected mesenchymal stem cells in unilateral ureteral obstruction-induced renal injury in rats. Materials and Methods: Male Wistar Albino rats (32 rats; weight, 250-300 g) were divided into 4 equal groups: group 1, control; group 2, unilateral ureteral obstruction; group 3, unilateral ureteral obstruction and mesenchymal stem cells; and group 4, unilateral ureteral obstruction and vascular endothelial growth factor-transfected mesenchymal stem cells. Vascular endothelial growth factor-transfected mesenchymal stem cells were administered intravenously before onset of unilateral ureteral obstruction. On day 14, the rats were killed and kidneys were retrieved. Tubular necrosis, mono-nuclear cell infiltration, and interstitial fibrosis were evaluated in paraffin blocks. We evaluated green fluorescent proteinpositive and vascular endothelial growth factorpositive cells; anti-inflammatory (Prostaglandin E2 Receptor) and interleukin 1 receptor antagonist), proinflammatory/anti-inflammatory (interleukin 6), and proinflammatory (MPO) cytokine expression levels; and levels of nitric oxide; transforming growth factor β1, E-cadherin, and hydroxyproline. Results: Green fluorescent protein-positive cells were negative in the renal parenchyma in groups 1 and 2 and positive in groups 3 and 4. Vascular endothelial growth factor levels were significantly higher in group 4. Transforming growth factor β1, nitric oxide, and E-cadherin levels were significantly higher in the unilateral ureteral obstruction than control group; however, in the study groups, these values were not significantly different from the unilateral ureteral obstruction group. In stem celltransplanted tissue samples, EP3, interleukin 1 receptor antagonist, and interleukin 6 levels were elevated, but MPO expression levels were low. Although there were significant differences for tubular necrosis and fibrosis in group 2, there were significant reductions in tubular injury and fibrosis in groups 3 and 4. Conclusions: Systemic stem cells transplanted into the kidney protected against unilateral ureteral obstruction-induced renal epithelial-mesenchymal transition and renal fibrosis.

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Mesenchymal Stem Cell: Does it Work in an Experimental Model with Acute Respiratory Distress Syndrome?

Cited by 13 publications

References 38 publications

Keratinocyte Growth Factor Promotes Epithelial Survival and Resolution in a Human Model of Lung Injury

Keratinocyte Growth Factor Promotes Epithelial Survival and Resolution in a Human Model of Lung Injury

Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep

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