Mesenchymal Cells and Bronchopulmonary Dysplasia: New Insights about the Dark Side of Oxygen.
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ABSTRACT:
SUBMITTER: Popova AP
PROVIDER: S-EPMC6503614 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Publications
Mesenchymal Cells and Bronchopulmonary Dysplasia: New Insights about the Dark Side of Oxygen.
American journal of respiratory cell and molecular biology 20190501 5
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Project description:Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants, leading to chronic respiratory disease. There has been an improvement in perinatal care, but many infants still suffer from impaired branching morphogenesis, alveolarization, and pulmonary capillary formation, causing lung function impairments and BPD. There is an increased risk of respiratory infections, pulmonary hypertension, and neurodevelopmental delays in infants with BPD, all of which can lead to long-term morbidity and mortality. Unfortunately, treatment options for Bronchopulmonary dysplasia are limited. A growing body of evidence indicates that mesenchymal stromal/stem cells (MSCs) can treat various lung diseases in regenerative medicine. MSCs are multipotent cells that can differentiate into multiple cell types, including lung cells, and possess immunomodulatory, anti-inflammatory, antioxidative stress, and regenerative properties. MSCs are regulated by mitochondrial function, as well as oxidant stress responses. Maintaining mitochondrial homeostasis will likely be key for MSCs to stimulate proper lung development and regeneration in Bronchopulmonary dysplasia. In recent years, MSCs have demonstrated promising results in treating and preventing bronchopulmonary dysplasia. Studies have shown that MSC therapy can reduce inflammation, mitochondrial impairment, lung injury, and fibrosis. In light of this, MSCs have emerged as a potential therapeutic option for treating Bronchopulmonary dysplasia. The article explores the role of MSCs in lung development and disease, summarizes MSC therapy's effectiveness in treating Bronchopulmonary dysplasia, and delves into the mechanisms behind this treatment.
| S-EPMC10642488 | biostudies-literature
Project description: Not available
| S-EPMC9872802 | biostudies-literature
Project description:Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, remains a major healthcare burden. Despite great progresses in perinatal medicine over the past decades, no cure for BPD has been found. The complex pathophysiology of the disease further hampers the development of effective treatment strategies, but recent insights into the biology of mesenchymal stem (MSCs) and progenitor cells in lung development and disease have ignited the hope of preventing or even treating BPD. The promising results of pre-clinical studies have lead to the first early phase clinical trials. However, these treatments are experimental and much more needs to be learned about the mechanism of action and manufacturing of MSCs. In this mini review, we briefly summarize the role of resident and exogenous MSCs in the development and treatment of BPD.
| S-EPMC4854850 | biostudies-literature
Project description:Bronchopulmonary dysplasia (BPD) frequently complicates preterm birth and leads to significant long-term morbidity. Unfortunately, few therapies are known to effectively prevent or treat BPD. Ongoing research has been focusing on potential therapies to limit inflammation in the preterm lung. In this review we highlight recent bench and clinical research aimed at understanding the role of inflammation in the pathogenesis of BPD. We also critically assess currently used therapies and promising developments in the field.
| S-EPMC3124103 | biostudies-other
Project description:ObjectivePreterm infants are at a high risk of developing BPD. Although progression in neonatal care has improved, BPD still causes significant morbidity and mortality, which can be attributed to the limited therapeutic choices for BPD. This review discusses the potential of MSC in treating BPD as well as their hurdles and possible solutions.Data sourcesThe search for data was not limited to any sites but was mostly performed on all clinical trials available in ClinicalTrials.gov as well as on PubMed by applying the following keywords: lung injury, preterm, inflammation, neonatal, bronchopulmonary dysplasia and mesenchymal stem cells.Study selectionsThe articles chosen for this review were collectively determined to be relevant and appropriate in discussing MSC not only as a potential treatment strategy for curbing the incidence of BPD but also including insights on problems regarding MSC treatment for BPD.ResultsClinical trials regarding the use of MSC for BPD had good results but also illustrated insights on problems to be addressed in the future regarding the treatment strategy. Despite that, the clinical trials had mostly favourable reviews.ConclusionWith BPD existing as a constant threat and there being no permanent solutions, the idea of regenerative medicine such as MSC may prove to be a breakthrough strategy when it comes to treating BPD. The success in clinical trials led to the formulation of prospective MSC-derived products such as PNEUMOSTEM®, and there is the possibility of a stem cell medication and permanent treatment for BPD in the near future.
| S-EPMC9527154 | biostudies-literature
Project description:Bronchopulmonary dysplasia (BPD) is a disease of prematurity related to the arrest of normal lung development. The objective of this study was to better understand how proteome modulation and cell-type shifts are noted in BPD pathology. Pediatric human donors aged 1-3 yr were classified based on history of prematurity and histopathology consistent with "healed" BPD (hBPD, n = 3) and "established" BPD (eBPD, n = 3) compared with respective full-term born (n = 6) age-matched term controls. Proteins were quantified by tandem mass spectroscopy with selected Western blot validations. Multiplexed immunofluorescence (MxIF) microscopy was performed on lung sections to enumerate cell types. Protein abundances and MxIF cell frequencies were compared among groups using ANOVA. Cell type and ontology enrichment were performed using an in-house tool and/or EnrichR. Proteomics detected 5,746 unique proteins, 186 upregulated and 534 downregulated, in eBPD versus control with fewer proteins differentially abundant in hBPD as compared with age-matched term controls. Cell-type enrichment suggested a loss of alveolar type I, alveolar type II, endothelial/capillary, and lymphatics, and an increase in smooth muscle and fibroblasts consistent with MxIF. Histochemistry and Western analysis also supported predictions of upregulated ferroptosis in eBPD versus control. Finally, several extracellular matrix components mapping to angiogenesis signaling pathways were altered in eBPD. Despite clear parsing by protein abundance, comparative MxIF analysis confirms phenotypic variability in BPD. This work provides the first demonstration of tandem mass spectrometry and multiplexed molecular analysis of human lung tissue for critical elucidation of BPD trajectory-defining factors into early childhood.NEW & NOTEWORTHY We provide new insights into the natural history of bronchopulmonary dysplasia in donor human lungs after the neonatal intensive care unit hospitalization. This study provides new insights into how the proteome and histopathology of BPD changes in early childhood, uncovering novel pathways for future study.
| S-EPMC10642360 | biostudies-literature
Project description:BACKGROUND:Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity and currently lacks efficient treatments. Mesenchymal stem/stromal cells (MSCs) have been extensively explored as a potential therapy in several preclinical and clinical settings. Human and animal MSCs have been shown to prevent and treat lung injury in various preclinical models of lung diseases, including experimental BPD. OBJECTIVES:To determine if MSCs, administered intravenously or endotracheally, are safe and effective in preventing or treating BPD, or both, in preterm infants. SEARCH METHODS:We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 10), MEDLINE via PubMed (1966 to 6 November 2016), Embase (1980 to 6 November 2016), and CINAHL (1982 to 6 November 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA:We considered RCTs and quasi-RCTs investigating prevention or treatment of BPD, or both, in preterm infants. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed trial quality according to prespecified criteria. MAIN RESULTS:We found no RCTs or quasi-RCTs addressing the use of MSCs for prevention or treatment of BPD in premature infants. Two RCTs are currently registered and ongoing. AUTHORS' CONCLUSIONS:There is insufficient evidence to determine the safety and efficacy of MSCs in the treatment or prevention of BPD in premature infants. The results of the ongoing trials addressing this issue are expected in the near future.
| S-EPMC6485972 | biostudies-literature
Project description:Advances in neonatal medicine have led to increased survival of infants born at the limits of viability, resulting in an increased incidence of bronchopulmonary dysplasia (BPD). BPD is a chronic lung disease of premature infants characterized by the arrest of alveolarization, fibroblast activation, and inflammation. BPD leads to significant morbidity and mortality in the neonatal period and is one of the leading causes of chronic lung disease in children. The past decade has brought a surge of trials investigating cellular therapies for the treatment of pulmonary diseases. Mesenchymal stem cells (MSCs) are of particular interest because of their ease of isolation, low immunogenicity, and anti-inflammatory and reparative properties. Clinical trials of MSCs have demonstrated short-term safety and tolerability; however, studies have also shown populations of MSCs with adverse pro-inflammatory and myofibroblastic characteristics. Cell-based therapies may represent the next breakthrough therapy for the treatment of BPD, however, there remain barriers to implementation as well as gaps in knowledge of the role of endogenous MSCs in the pathogenesis of BPD. Concurrent high-quality basic science, translational, and clinical studies investigating the fundamental pathophysiology underlying BPD, therapeutic mechanisms of exogenous MSCs, and logistics of translating cellular therapies will be important areas of future research.
| S-EPMC5895100 | biostudies-literature
Project description:In the United States, approximately 12,000 preterm infants are diagnosed with bronchopulmonary dysplasia (BPD) and many of these infants require supplemental oxygen after initial hospital discharge. In children with BPD we sought to identify factors associated with supplemental oxygen use after initial hospital discharge, factors associated with duration of supplemental oxygen use, and methods used to wean off supplemental oxygen in the home environment.All subjects (n = 420) with the diagnosis of BPD were recruited from a single center Bronchopulmonary Dysplasia Clinic between 2008 and 2013. Subject information was obtained from patient history records, patient demographics, and caregiver questionnaires.Younger gestational age and having a Nissen fundoplication were associated with home supplemental oxygen use in subjects with BPD. Of the 154 subjects who received supplemental oxygen at home, 38% received flows ≤1/8 LPM, 30% received flows >1/8 LPM and ≤1/4 LPM, 21% received flows >1/4 LPM and ≤1/2 LPM, and 11% received flows >1/2 LPM. Among subjects receiving ≤1/8 LPM of oxygen, the median age of weaning off oxygen was 10.1 months, but increased depending on level of oxygen flow at initial outpatient visit. Of the 137 subjects weaned off of oxygen during the study period, weaning was not supervised by a physician in 32.1% of subjects.Home supplemental oxygen use is common in infants diagnosed with BPD. In this study, the median age of weaning off supplemental oxygen was 10.1 months after initial hospital discharge. Unsupervised weaning of supplemental oxygen occurred in 32.1% of subjects with BPD. Pediatr Pulmonol. 2016;51:1206-1211. © 2016 Wiley Periodicals, Inc.
| S-EPMC5556369 | biostudies-other
Project description:Aberrant remodelling of the extracellular matrix in the developing lung may underlie arrested alveolarisation associated with bronchopulmonary dysplasia (BPD). Transglutaminases are regulators of extracellular matrix remodelling. Therefore, the expression and activity of transglutaminases were assessed in lungs from human neonates with BPD and in a rodent model of BPD. Transglutaminase expression and localisation were assessed by RT-PCR, immunoblotting, activity assay and immunohistochemical analyses of human and mouse lung tissues. Transglutaminase regulation by transforming growth factor (TGF)-β was investigated in lung cells by luciferase-based reporter assay and RT-PCR. TGF-β signalling was neutralised in vivo in an animal model of BPD, to determine whether TGF-β mediated the hyperoxia-induced changes in transglutaminase expression. Transglutaminase 2 expression was upregulated in the lungs of preterm infants with BPD and in the lungs of hyperoxia-exposed mouse pups, where lung development was arrested. Transglutaminase 2 localised to the developing alveolar septa. TGF-β was identified as a regulator of transglutaminase 2 expression in human and mouse lung epithelial cells. In vivo neutralisation of TGF-β signalling partially restored normal lung structure and normalised lung transglutaminase 2 mRNA expression. Our data point to a role for perturbed transglutaminase 2 activity in the arrested alveolarisation associated with BPD.
| S-EPMC4212268 | biostudies-literature