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GFP-labeled mouse stem cells in the lung tissue. GFPlabeled hematopoietic stem cells (HPSCs) were not detected in the lung parenchyma of a ErbB4 heart+/− or b ErbB4 heart−/− lungs, but GFP-labeled bone marrow-derived mesenchymal stem cells (BMSCs) were sporadically detected in c ErbB4 heart+/ − or d ErbB4 heart−/− lungs 24 h
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ErbB4 is a regulator in lung development and disease. Prenatal infection is an important risk factor for the delay of morphologic lung development, while promoting the maturation of the surfactant system. Bone marrow–derived mesenchymal stem cells (BMSCs) have the potential to prevent lung injury. We hypothesized that BMSCs in comparison with hemat...
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Context 1
... cytometry used for cell surface phenotype analyses indicated that the BMSCs were highly positive for the Sca-1 and for CD29 and negative for CD31 and CD73 (Fig. 3a, b). No GFPpositive HPSCs (Fig. 4a, b), but GFP-positive mouse BMSCs (Fig. 4c, d) were detected 24 h after intraamniotic injection in fetal lung sections at gd ...
Context 2
... cytometry used for cell surface phenotype analyses indicated that the BMSCs were highly positive for the Sca-1 and for CD29 and negative for CD31 and CD73 (Fig. 3a, b). No GFPpositive HPSCs (Fig. 4a, b), but GFP-positive mouse BMSCs (Fig. 4c, d) were detected 24 h after intraamniotic injection in fetal lung sections at gd ...
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The use of cell therapies has recently increased for the treatment of pulmonary diseases. Mesenchymal stem/stromal cells (MSCs) and alveolar type II cells (ATII) are the main cell-based therapies used for the treatment of acute respiratory distress syndrome (ARDS). Many pre-clinical studies have shown that both therapies generate positive outcomes;...
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... In rodent models, fetal exposure to infectious stimuli was mostly induced between the late canalicular and saccular stage [58][59][60]65,[68][69][70][71][72][73][74]80], and a few were as early as in the pseudoglandular stage [40,[61][62][63][64]66,67,79], mimicking acute and prolonged prenatal infections, respectively. The serotype and dose of LPS vary widely among studies, with the latter ranging from 1 to 10 µg/amniotic sac for rats and 100 pg to 4 µg/amniotic sac and 0.08 to 1 mg/kg i.p. for mice, respectively [40,[57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74]. ...
... In rodent models, fetal exposure to infectious stimuli was mostly induced between the late canalicular and saccular stage [58][59][60]65,[68][69][70][71][72][73][74]80], and a few were as early as in the pseudoglandular stage [40,[61][62][63][64]66,67,79], mimicking acute and prolonged prenatal infections, respectively. The serotype and dose of LPS vary widely among studies, with the latter ranging from 1 to 10 µg/amniotic sac for rats and 100 pg to 4 µg/amniotic sac and 0.08 to 1 mg/kg i.p. for mice, respectively [40,[57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74]. In addition, the i.a. ...
... In addition, the i.a. injection volume of LPS varied between 5 and 200 µL/amniotic sac [57][58][59]71,72,74]. This represents an important but largely underappreciated confounding factor. ...
Intra-amniotic infection (IAI) is one major driver for preterm birth and has been demonstrated by clinical studies to exert both beneficial and injurious effects on the premature lung, possibly due to heterogeneity in the microbial type, timing, and severity of IAI. Due to the inaccessibility of the intra-amniotic cavity during pregnancies, preclinical animal models investigating pulmonary consequences of IAI are indispensable to elucidate the pathogenesis of bronchopulmonary dysplasia (BPD). It is postulated that on one hand imbalanced inflammation, orchestrated by lung immune cells such as macrophages, may impact on airway epithelium, vascular endothelium, and interstitial mesenchyme, resulting in abnormal lung development. On the other hand, excessive suppression of inflammation may as well cause pulmonary injury and a certain degree of inflammation is beneficial. So far, effective strategies to prevent and treat BPD are scarce. Therapeutic options targeting single mediators in signaling cascades and mesenchymal stromal cells (MSCs)-based therapies with global regulatory capacities have demonstrated efficacy in preclinical animal models and warrant further validation in patient populations. Ante-, peri- and postnatal exposome analysis and therapeutic investigations using multiple omics will fundamentally dissect the black box of IAI and its effect on the premature lung, contributing to precisely tailored and individualized therapies.
... The initial study results were in the meantime reproduced in overall 28 subsequent studies applying mesenchymal stem cells from different origin [27,28,. Study designs, key findings, follow-up investigations for safety and efficacy and details on origin, dosage, time point and route of MSC administration are presented within Table 2. Comparable results were obtained when lipopolysaccharide was applied mimicking the situation of amniotic infection or when hyperoxia was preceded by lipopolysaccharide exposure (for details see Table 3) [57][58][59]. Both prenatal and postnatal application of MSC proved therapeutic efficacy [57][58][59]. ...
... Study designs, key findings, follow-up investigations for safety and efficacy and details on origin, dosage, time point and route of MSC administration are presented within Table 2. Comparable results were obtained when lipopolysaccharide was applied mimicking the situation of amniotic infection or when hyperoxia was preceded by lipopolysaccharide exposure (for details see Table 3) [57][58][59]. Both prenatal and postnatal application of MSC proved therapeutic efficacy [57][58][59]. ...
Bronchopulmonary dysplasia (BPD) remains one of the most devastating consequences of preterm birth resulting in life-long restrictions in lung function. Distorted lung development is caused by its inflammatory response which is mainly provoked by mechanical ventilation, oxygen toxicity and bacterial infections. Dysfunction of resident lung mesenchymal stem cells (MSC) represents one key hallmark that drives BPD pathology. Despite all progress in the understanding of pathomechanisms, therapeutics to prevent or treat BPD are to date restricted to a few drugs. The limited therapeutic efficacy of established drugs can be explained by the fact that they fail to concurrently tackle the broad spectrum of disease driving mechanisms and by the huge overlap between distorted signal pathways of lung development and inflammation. The great enthusiasm about MSC based therapies as novel therapeutic for BPD arises from the capacity to inhibit inflammation while simultaneously promoting lung development and repair. Preclinical studies, mainly performed in rodents, raise hopes that there will be finally a broadly acting, efficient therapy at hand to prevent or treat BPD. Our narrative review gives a comprehensive overview on preclinical achievements, results from first early phase clinical studies and challenges to a successful translation into the clinical setting.
