Dataset Information

Mesenchymal stem cell therapy for laryngotracheal stenosis: A systematic review of preclinical studies.

ABSTRACT:

Background

Laryngotracheal stenosis (LTS) can be either congenital or acquired. Laryngeal stenosis is most often encountered after prolonged intubation. The mechanism for stenosis following intubation is believed to be hypertrophic scarring. Mesenchymal stem cells (MSCs) therapy has shown promising results in regenerative medicine. We aimed to systematically review the literature on MSC therapy for stenosis of the conductive airways.

Methods

PubMed, EMBASE, Google Scholar and the Cochrane Library were systematically searched from January 1980-January 2017 with the purpose of identifying all studies addressing the effect of MSC therapy on the airway. We assessed effect on inflammation, fibrosis, and MSC as a component in tissue engineering for treating defects in the airway.

Results

We identified eleven studies (n = 256 animals) from eight countries evaluating the effect of MSCs as a regenerative therapy in the upper airways. The studies indicate that MSC therapy may lead to a more constructive inflammatory response as well as support tissue regeneration.

Conclusion

There may be a favorable effect of MSCs in inhibiting inflammation and as a component in tissue engineering. Given the heterogeneous nature of the included animal studies, any clear conclusion regarding the effect of tracheal stenosis in human subjects cannot be drawn. The included preclinical studies are however encouraging for further research.

SUBMITTER: Jakobsen KK

PROVIDER: S-EPMC5608394 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Mesenchymal stem cell therapy for laryngotracheal stenosis: A systematic review of preclinical studies.

Jakobsen Kathrine Kronberg KK Grønhøj Christian C Jensen David H DH Fischer-Nielsen Anne A Hjuler Thomas T von Buchwald Christian C

PloS one 20170921 9

<h4>Background</h4>Laryngotracheal stenosis (LTS) can be either congenital or acquired. Laryngeal stenosis is most often encountered after prolonged intubation. The mechanism for stenosis following intubation is believed to be hypertrophic scarring. Mesenchymal stem cells (MSCs) therapy has shown promising results in regenerative medicine. We aimed to systematically review the literature on MSC therapy for stenosis of the conductive airways.<h4>Methods</h4>PubMed, EMBASE, Google Scholar and the ...[more]

PMID: 28934345

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Project description:BackgroundParaquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy.MethodsThe electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed.ResultsEleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1β, TNF-α and TGF-β1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found.ConclusionMSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.

Project description:Extreme prematurity is the leading cause of death among children under 5 years of age. Currently, there is no treatment for bronchopulmonary dysplasia (BPD), the most common complication of extreme prematurity. Experimental studies in animal models of BPD suggest that mesenchymal stromal cells (MSCs) are lung protective. To date, no systematic review and meta-analysis has evaluated the preclinical evidence of this promising therapy. Our protocol was registered with Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies prior to searching MEDLINE (1946 to June 1, 2015), Embase (1947 to 2015 Week 22), Pubmed, Web of Science, and conference proceedings (1990 to present) for controlled comparative studies of neonatal animal models that received MSCs or cell free MSC-derived conditioned media (MSC-CM). Lung alveolarization was the primary outcome. We used random effects models for data analysis and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. We screened 990 citations; 25 met inclusion criteria. All used hyperoxia-exposed neonatal rodents to model BPD. MSCs significantly improved alveolarization (Standardized mean difference of -1.330, 95% confidence interval [CI -1.724, -0.94, I2 69%]), irrespective of timing of treatment, source, dose, or route of administration. MSCs also significantly ameliorated pulmonary hypertension, lung inflammation, fibrosis, angiogenesis, and apoptosis. Similarly, MSC-CM significantly improved alveolarization, angiogenesis, and pulmonary artery remodeling. MSCs, tested exclusively in hyperoxic rodent models of BPD, show significant therapeutic benefit. Unclear risk of bias and incomplete reporting in the primary studies highlights nonadherence to reporting standards. Overall, safety and efficacy in other species/large animal models may provide useful information for guiding the design of clinical trials. Stem Cells Translational Medicine 2017;6:2079-2093.

Project description:Laryngotracheal stenosis is an obstructive respiratory disease that leads to voicing difficulties and dyspnea with potential life-threatening consequences. The majority of incidences are due to iatrogenic etiology from endotracheal tube intubation; however, airway scarring also has idiopathic causes. While recent evidence suggests a microbial contribution to mucosal inflammation, the microbiota associated with different types of stenosis has not been characterized. High-throughput sequencing of the V4 region of the16S rRNA gene was performed to characterize the microbial communities of 61 swab samples from 17 iatrogenic and 10 adult idiopathic stenosis patients. Nonscar swabs from stenosis patients were internal controls, and eight swabs from four patients without stenosis represented external controls. Significant differences in diversity were observed between scar and nonscar samples and among sample sites, with decreased diversity detected in scar samples and the glottis region. Permutational analysis of variance (PERMANOVA) results revealed significant differences in community composition for scar versus nonscar samples, etiology type, sample site, groups (iatrogenic, idiopathic, and internal and external controls), and individual patients. Pairwise Spearman's correlation revealed a strong inverse correlation between Prevotella and Streptococcus among all samples. Finally, bacteria in the family Moraxellaceae were found to be distinctly associated with idiopathic stenosis samples in comparison with external controls. Our findings suggest that specific microbiota and community shifts are present with laryngotracheal stenosis in adults, with members of the family Moraxellaceae, including the known pathogens Moraxella and Acinetobacter, identified in idiopathic scar. Further work is warranted to elucidate the contributing role of bacteria on the pathogenesis of laryngotracheal stenosis.IMPORTANCE The laryngotracheal region resides at the intersection between the heavily studied nasal cavity and lungs; however, examination of the microbiome in chronic inflammatory conditions of the subglottis and trachea remains scarce. To date, studies have focused on the microbiota of the vocal folds, or the glottis, for laryngeal carcinoma, as well as healthy larynges, benign vocal fold lesions, and larynges exposed to smoking and refluxate. In this study, we seek to examine the structure and composition of the microbial community in adult laryngotracheal stenosis of various etiologies. Due to the heterogeneity among the underlying pathogenesis mechanisms and clinical outcomes seen in laryngotracheal stenosis disease, we hypothesized that different microbial profiles will be detected among various stenosis etiology types. Understanding differences in the microbiota for subglottic stenosis subtypes may shed light upon etiology-specific biomarker identification and offer novel insights into management approaches for this debilitating disease.

Dataset Information

Mesenchymal stem cell therapy for laryngotracheal stenosis: A systematic review of preclinical studies.

Background

Methods

Results

Conclusion

Publications

Mesenchymal stem cell therapy for laryngotracheal stenosis: A systematic review of preclinical studies.

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