Mesenchymal Stromal Cell Therapy in Bronchopulmonary Dysplasia: Systematic Review and Meta‐Analysis of Preclinical Studies

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...

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Veröffentlicht in:Stem cells translational medicine 2017-12, Vol.6 (12), p.2079-2093
Hauptverfasser: Augustine, Sajit, Avey, Marc T., Harrison, Brittany, Locke, Tiffany, Ghannad, Mona, Moher, David, Thébaud, Bernard
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Sprache:eng
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Zusammenfassung: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 MSCs in pre‐clinical bronchopulmonary dysplasia (BPD). In this first‐ever systematic review and meta‐analysis, when tested exclusively in hyperoxic rodent models of BPD, mesenchymal stromal cells significantly improved several outcome measures, although with a high degree of heterogeneity, unclear risk of bias, poor reporting and potential publication bias; underscoring the need to fix methodological flaws by rigorously implementing reporting standards such as Animal Research: Reporting of I
ISSN:2157-6564
2157-6580
2157-6580
DOI:10.1002/sctm.17-0126