4.5 Article

Bone Marrow Mononuclear Cell Therapy Led to Alveolar-Capillary Membrane Repair, Improving Lung Mechanics in Endotoxin-Induced Acute Lung Injury

Journal

CELL TRANSPLANTATION
Volume 19, Issue 8, Pages 965-971

Publisher

SAGE PUBLICATIONS INC
DOI: 10.3727/096368910X506845

Keywords

Lung mechanics; Bone marrow-derived mononuclear cells (BMDMC); Electron microscopy; Inflammation

Funding

  1. Centers of Excellence Program (PRONEX-FAPERJ)
  2. Brazilian Council for Scientific and Technological Development (CNPq)
  3. Carlos Chagas Filho
  4. Rio de Janeiro State Research Supporting Foundation (FAPERJ)
  5. Sao Paulo State Research Supporting Foundation (FAPESP)

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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 injur;y (ALI) group, Escherichia coli lipopolysaccharide (LPS) was instilled intratracheally (40 mu g, IT), and control (C) mice received saline (0.05 ml, IT). One hour after the administration of saline or LPS, BMDMC (2 x 10(7) cells) was intravenously injected. At day 28, animals were anesthetized and lung mechanics [static elastance (E-st), resistive (Delta P-1), and viscoelastic (Delta P-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, Delta P-1, and Delta P-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.

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