title: Bone marrow mononuclear cell therapy led to alveolar-capillary membrane repair, improving lung mechanics in endotoxin-induced acute lung injury.
abstract: The aim of this study was to test the hypothesis that bone marrow mononuclear cell (BMDMC) therapy led an improvement in lung mechanics and histology in endotoxin-induced lung injury. Twenty-four C57BL/6 mice were randomly divided into four groups (n = 6 each). In the acute lung injury (ALI) group, Escherichia coli lipopolysaccharide (LPS) was instilled intratracheally (40 μg, IT), and control (C) mice received saline (0.05 ml, IT). One hour after the administration of saline or LPS, BMDMC (2 × 10(7) cells) was intravenously injected. At day 28, animals were anesthetized and lung mechanics [static elastance (E(st)), resistive (ΔP(1)), and viscoelastic (ΔP(2)) pressures] and histology (light and electron microscopy) were analyzed. Immunogold electron microscopy was used to evaluate if multinucleate cells were type II epithelial cells. BMDMC therapy prevented endotoxin-induced lung inflammation, alveolar collapse, and interstitial edema. In addition, BMDMC administration led to epithelial and endothelial repair with multinucleated type II pneumocytes. These histological changes yielded a reduction in lung E(st), ΔP(1), and ΔP(2) compared to ALI. In the present experimental ALI model, the administration of BMDMC yielded a reduction in the inflammatory process and a repair of epithelium and endothelium, reducing the amount of alveolar collapse, thus leading to an improvement in lung mechanics.
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luiz Felipe M
authors.initials: LF
authors.lastname: Prota
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Lassance
authors.forename: Tatiana
authors.initials: T
authors.lastname: Maron-Gutierrez
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Castiglione
authors.forename: Cristiane Souza Baez
authors.initials: CS
authors.lastname: Garcia
authors.forename: Maria Cristina Ebole
authors.initials: MC
authors.lastname: Santana
authors.forename: Jackson
authors.initials: J
authors.lastname: Souza-Menezes
authors.forename: Soraia C
authors.initials: SC
authors.lastname: Abreu
authors.forename: Vivian
authors.initials: V
authors.lastname: Samoto
authors.forename: Marcelo Felipe
authors.initials: MF
authors.lastname: Santiago
authors.forename: Vera Luiza
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Christina Maeda
authors.initials: CM
authors.lastname: Takiya
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D000818:Animals; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity; D004847:Epithelial Cells / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006046:Gold / Q000737:chemistry; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission
chemical_list: D004731:Endotoxins; D006046:Gold