Bone marrow-derived mononuclear cell therapy in experimental pulmonary and extrapulmonary acute lung injury.
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.
Araújo
Indianara M
IM
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Abreu
Soraia C
SC
Maron-Gutierrez
Tatiana
T
Cruz
Fernanda
F
Fujisaki
Livia
L
Carreira
Humberto
H
Ornellas
Felipe
F
Ornellas
Debora
D
Vieira-de-Abreu
Adriana
A
Castro-Faria-Neto
Hugo C
HC
Muxfeldt Ab'Saber
Alexandre
A
Teodoro
Walcy R
WR
Diaz
Bruno L
BL
Peres Dacosta
Carlos
C
Capelozzi
Vera L
VL
Pelosi
Paolo
P
Morales
Marcelo M
MM
Rocco
Patricia R M
PR
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
D016207:Cytokines; D008070:Lipopolysaccharides; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053148:Caspase 3