The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index.
Prevention of LPS-Induced Acute Lung Injury in Mice by Mesenchymal Stem Cells Overexpressing Angiopoietin 1
Open accessAbstract
BACKGROUND: The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. ALI is characterized by disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema associated with a proteinaceous alveolar exudate. Current specific treatment strategies for ALI/ARDS are lacking. We hypothesized that mesenchymal stem cells (MSCs), with or without transfection with the vasculoprotective gene angiopoietin 1 (ANGPT1) would have beneficial effects in experimental ALI in mice. METHODS AND FINDINGS: Syngeneic MSCs with or without transfection with plasmid containing the human ANGPT1 gene (pANGPT1) were delivered through the right jugular vein of mice 30 min after intratracheal instillation of lipopolysaccharide (LPS) to induce lung injury. Administration of MSCs significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluid (53%, 95% confidence interval [CI] 7%-101%; and 60%, CI 4%-116%, respectively) as well as reducing levels of proinflammatory cytokines in both BAL fluid and lung parenchymal homogenates. Furthermore, administration of MSCs transfected with pANGPT1 resulted in nearly complete reversal of LPS-induced increases in lung permeability as assessed by reductions in IgM and albumin levels in BAL (96%, CI 6%-185%; and 74%, CI 23%-126%, respectively). Fluorescently tagged MSCs were detected in the lung tissues by confocal microscopy and flow cytometry in both naïve and LPS-injured animals up to 3 d. CONCLUSIONS: Treatment with MSCs alone significantly reduced LPS-induced acute pulmonary inflammation in mice, while administration of pANGPT1-transfected MSCs resulted in a further improvement in both alveolar inflammation and permeability. These results suggest a potential role for cell-based ANGPT1 gene therapy to treat clinical ALI/ARDS.
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Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis
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Requisite Role of Angiopoietin-1, a Ligand for the TIE2 Receptor, during Embryonic Angiogenesis
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Cited by
Islam, M. N., Das, S. R., Emin, M. T., Wei, M., Sun, L., Westphalen, K., Rowlands, D. J., Quadri, S. K., Bhattacharya, S., & Bhattacharya, J. (2012) · Nature Medicine · doi:10.1038/nm.2736 · Cited by 1,585
In Search of the In Vivo Identity of Mesenchymal Stem Cells
da Silva Meirelles, L., Caplan, A. I., & Nardi, N. B. (2008) · Stem Cells · doi:10.1634/stemcells.2007-1122 · Cited by 1,077
Mei, S. H. J., Haitsma, J. J., Dos Santos, C. C., Deng, Y., Lai, P. F. H., Slutsky, A. S., Liles, W. C., & Stewart, D. J. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201001-0010oc · Cited by 721
Self-citationLee, J. W., Fang, X., Gupta, N., Serikov, V., & Matthay, M. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907996106 · Cited by 715
Zhu, Y.-G., Feng, X.-M., Abbott, J., Fang, X.-H., Hao, Q., Monsel, A., Qu, J.-M., Matthay, M. A., & Lee, J. W. (2014) · Stem Cells · doi:10.1002/stem.1504 · Cited by 688
Metadata
- Authors
- Mei, S. H. J., McCarter, S. D., Deng, Y., Parker, C. H., Liles, W. C., & Stewart, D. J.
- Venue
- PLoS Medicine
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-09-04
- Volume
- 4
- Issue
- 9
- Pages
- e269
- ISSN
- 1549-1277 (ISSN-L)
- 1549-1676
- OpenAlex
- W2085030928
- Cited by
- 619
- References
- 75
- FWCI
- 11.85
- Type
- journal article
- Language
- en
- Open access
- gold
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