title: Bone marrow-derived mononuclear cell therapy in experimental pulmonary and extrapulmonary acute lung injury.
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.
  
  
  METHODS
  Prospective, randomized, controlled, experimental study.
  
  
  METHODS
  University research laboratory.
  
  
  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.
  
  
  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.
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Indianara M
authors.initials: IM
authors.lastname: Araújo
authors.forename: Soraia C
authors.initials: SC
authors.lastname: Abreu
authors.forename: Tatiana
authors.initials: T
authors.lastname: Maron-Gutierrez
authors.forename: Fernanda
authors.initials: F
authors.lastname: Cruz
authors.forename: Livia
authors.initials: L
authors.lastname: Fujisaki
authors.forename: Humberto
authors.initials: H
authors.lastname: Carreira
authors.forename: Felipe
authors.initials: F
authors.lastname: Ornellas
authors.forename: Debora
authors.initials: D
authors.lastname: Ornellas
authors.forename: Adriana
authors.initials: A
authors.lastname: Vieira-de-Abreu
authors.forename: Hugo C
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.forename: Alexandre
authors.initials: A
authors.lastname: Muxfeldt Ab'Saber
authors.forename: Walcy R
authors.initials: WR
authors.lastname: Teodoro
authors.forename: Bruno L
authors.initials: BL
authors.lastname: Diaz
authors.forename: Carlos
authors.initials: C
authors.lastname: Peres Dacosta
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004926:Escherichia coli; D005260:Female; D007963:Leukocytes, Mononuclear / Q000637:transplantation; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D012016:Reference Values; D015656:Respiratory Mechanics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053148:Caspase 3