| Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats. | |
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MedLine Citation:
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PMID: 19713449 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: Bronchopulmonary dysplasia (BPD) and emphysema are characterized by arrested alveolar development or loss of alveoli; both are significant global health problems and currently lack effective therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) prevent adult lung injury, but their therapeutic potential in neonatal lung disease is unknown. OBJECTIVES: We hypothesized that intratracheal delivery of BMSCs would prevent alveolar destruction in experimental BPD. METHODS: In vitro, BMSC differentiation and migration were assessed using co-culture assays and a modified Boyden chamber. In vivo, the therapeutic potential of BMSCs was assessed in a chronic hyperoxia-induced model of BPD in newborn rats. MEASUREMENTS AND MAIN RESULTS: In vitro, BMSCs developed immunophenotypic and ultrastructural characteristics of type II alveolar epithelial cells (AEC2) (surfactant protein C expression and lamellar bodies) when co-cultured with lung tissue, but not with culture medium alone or liver. Migration assays revealed preferential attraction of BMSCs toward oxygen-damaged lung versus normal lung. In vivo, chronic hyperoxia in newborn rats led to air space enlargement and loss of lung capillaries, and this was associated with a decrease in circulating and resident lung BMSCs. Intratracheal delivery of BMSCs on Postnatal Day 4 improved survival and exercise tolerance while attenuating alveolar and lung vascular injury and pulmonary hypertension. Engrafted BMSCs coexpressed the AEC2-specific marker surfactant protein C. However, engraftment was disproportionately low for cell replacement to account for the therapeutic benefit, suggesting a paracrine-mediated mechanism. In vitro, BMSC-derived conditioned medium prevented O(2)-induced AEC2 apoptosis, accelerated AEC2 wound healing, and enhanced endothelial cord formation. CONCLUSIONS: BMSCs prevent arrested alveolar and vascular growth in part through paracrine activity. Stem cell-based therapies may offer new therapeutic avenues for lung diseases that currently lack efficient treatments. |
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Authors:
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Timothy van Haaften; Roisin Byrne; Sebastien Bonnet; Gael Y Rochefort; John Akabutu; Manaf Bouchentouf; Gloria J Rey-Parra; Jacques Galipeau; Alois Haromy; Farah Eaton; Ming Chen; Kyoko Hashimoto; Doris Abley; Greg Korbutt; Stephen L Archer; Bernard Thébaud |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-08-27 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 180 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-20 Completed Date: 2009-12-07 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 1131-42 Citation Subset: AIM; IM |
Affiliation:
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Department of Pediatrics, Women and Children Health Research Institute, University of Alberta, Edmonton, Alberta, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Bone Marrow Cell Culture Techniques Disease Models, Animal Exercise Tolerance Hyperoxia Hypertension, Pulmonary / prevention & control Lung Injury / prevention & control* Mesenchymal Stem Cells* Pulmonary Alveoli / growth & development*, ultrastructure Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction Survival Analysis |
| Grant Support | |
ID/Acronym/Agency:
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R01-HL071115/HL/NHLBI NIH HHS; //Canadian Institutes of Health Research |
| Comments/Corrections | |
Comment In:
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Am J Respir Crit Care Med. 2009 Dec 1;180(11):1039-41
[PMID:
19923401
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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