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Mesenchymal Stem Cell Microvesicles Attenuate Acute Lung Injury in Mice Partly Mediated by Ang-1 mRNA.
- Source :
-
Stem cells (Dayton, Ohio) [Stem Cells] 2017 Jul; Vol. 35 (7), pp. 1849-1859. Date of Electronic Publication: 2017 Apr 24. - Publication Year :
- 2017
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Abstract
- Microvesicles (MVs) derived from human mesenchymal stem cells (MSC MVs) were demonstrated to ameliorate inflammation in lungs. We have found their content of mRNA for keratinocyte growth factor was partly involved in their therapeutic effects. As MSC MVs also contained a substantial quantity of angiopoietin-1 (Ang-1) mRNA, which plays an essential role in vascular stabilization and resolving inflammation, we hypothesized that Ang-1 mRNA might similarly account for a part of their therapeutic effects. We downregulated Ang-1 mRNA expression in MVs, using a lentivirus vector carrying Ang-1 short hairpin RNA to transfect MSCs. A mouse model of lipopolysaccharide induced acute lung injury (ALI) was used in vivo. We also studied in vitro interactions between Ang-1 mRNA deficient MVs on macrophages and human lung microvascular endothelial cells. Compared with negative control, Ang-1 mRNA deficient MVs increased the influx of neutrophils and macrophage inflammatory protein-2 levels in bronchoalveolar lavage fluid by 136% and 105%, respectively, suggesting a deteriorative lung inflammation and a failure to restore pulmonary capillary permeability assessed by Evan's blue dye and bronchoalveolar lavage albumin level. In vitro, the addition of Ang-1 mRNA deficient MVs failed to maintain the integrity of endotoxin-stimulated microvascular endothelial cells and abrogated the decrease in tumor necrosis factor-α level and the increase in interleukin-10 level mediated by negative control in RAW 264.7 cells. In summary, the therapeutic effects of MVs in ALI, and their immunomodulatory properties on macrophages were partly mediated through their content of Ang-1 mRNA. Stem Cells 2017;35:1849-1859.<br /> (© 2017 AlphaMed Press.)
- Subjects :
- Acute Lung Injury chemically induced
Acute Lung Injury genetics
Acute Lung Injury pathology
Angiopoietin-1 antagonists & inhibitors
Angiopoietin-1 metabolism
Animals
Bronchoalveolar Lavage Fluid chemistry
Capillary Permeability genetics
Cell-Derived Microparticles chemistry
Cell-Derived Microparticles transplantation
Chemokine CXCL2 genetics
Chemokine CXCL2 metabolism
Disease Models, Animal
Endothelial Cells cytology
Endothelial Cells metabolism
Gene Expression Regulation
Humans
Interleukin-10 genetics
Interleukin-10 metabolism
Lipopolysaccharides
Lung pathology
Male
Mesenchymal Stem Cells cytology
Mice
Mice, Inbred C57BL
Neutrophil Infiltration genetics
Neutrophils metabolism
Neutrophils pathology
Primary Cell Culture
RNA, Messenger antagonists & inhibitors
RNA, Messenger metabolism
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Signal Transduction
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha metabolism
Acute Lung Injury prevention & control
Angiopoietin-1 genetics
Cell-Derived Microparticles metabolism
Lung metabolism
Mesenchymal Stem Cells metabolism
RNA, Messenger genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1549-4918
- Volume :
- 35
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Stem cells (Dayton, Ohio)
- Publication Type :
- Academic Journal
- Accession number :
- 28376568
- Full Text :
- https://doi.org/10.1002/stem.2619