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Bone marrow-derived mononuclear cell therapy in experimental pulmonary and extrapulmonary acute lung injury.
- Source :
-
Critical care medicine [Crit Care Med] 2010 Aug; Vol. 38 (8), pp. 1733-41. - Publication Year :
- 2010
-
Abstract
- Objective: To hypothesize that bone marrow-derived mononuclear cell (BMDMC) therapy might act differently on lung and distal organs in models of pulmonary or extrapulmonary acute lung injury with similar mechanical compromises. The pathophysiology of acute lung injury differs according to the type of primary insult.<br />Design: Prospective, randomized, controlled, experimental study.<br />Setting: University research laboratory.<br />Measurements and Main Results: In control animals, sterile saline solution was intratracheally (0.05 mL) or intraperitoneally (0.5 mL) injected. Acute lung injury animals received Escherichia coli lipopolysaccharide intratracheally (40 microg, ALIp) or intraperitoneally (400 microg, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALIexp animals were further randomized into subgroups receiving saline (0.05 mL) or BMDMC (2 x 10) intravenously. On day 7, BMDMC led to the following: 1) increase in survival rate; 2) reduction in static lung elastance, alveolar collapse, and bronchoalveolar lavage fluid cellularity (higher in ALIexp than ALIp); 3) decrease in collagen fiber content, cell apoptosis in lung, kidney, and liver, levels of interleukin-6, KC (murine interleukin-8 homolog), and interleukin-10 in bronchoalveolar lavage fluid, and messenger RNA expression of insulin-like growth factor, platelet-derived growth factor, and transforming growth factor-beta in both groups, as well as repair of basement membrane, epithelium and endothelium, regardless of acute lung injury etiology; 4) increase in vascular endothelial growth factor levels in bronchoalveolar lavage fluid and messenger RNA expression in lung tissue in both acute lung injury groups; and 5) increase in number of green fluorescent protein-positive cells in lung, kidney, and liver in ALIexp.<br />Conclusions: BMDMC therapy was effective at modulating the inflammatory and fibrogenic processes in both acute lung injury models; however, survival and lung mechanics and histology improved more in ALIexp. These changes may be attributed to paracrine effects balancing pro- and anti-inflammatory cytokines and growth factors, because a small degree of pulmonary BMDMC engraftment was observed.
- Subjects :
- Acute Lung Injury chemically induced
Acute Lung Injury mortality
Acute Lung Injury physiopathology
Animals
Bronchoalveolar Lavage Fluid cytology
Caspase 3 metabolism
Disease Models, Animal
Escherichia coli
Female
Leukocytes, Mononuclear transplantation
Lipopolysaccharides
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Confocal
Microscopy, Electron
Platelet-Derived Growth Factor metabolism
RNA, Messenger metabolism
Random Allocation
Reference Values
Reverse Transcriptase Polymerase Chain Reaction
Survival Rate
Transforming Growth Factor beta metabolism
Acute Lung Injury therapy
Apoptosis physiology
Bone Marrow Transplantation methods
Cytokines metabolism
Respiratory Mechanics physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0293
- Volume :
- 38
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Critical care medicine
- Publication Type :
- Academic Journal
- Accession number :
- 20562701
- Full Text :
- https://doi.org/10.1097/CCM.0b013e3181e796d2