title: Effects of bone marrow-derived mononuclear cells from healthy or acute respiratory distress syndrome donors on recipient lung-injured mice.
abstract: OBJECTIVE
  The advantage of using autologous bone marrow-derived mononuclear cells to treat acute respiratory distress syndrome patients is to prevent immunological rejection. However, bone marrow-derived mononuclear cells may be altered by different acute respiratory distress syndrome etiologies, resulting in questionable efficacy and thus limited clinical application. We aimed to investigate the effects of bone marrow-derived mononuclear cells obtained from healthy and acute respiratory distress syndrome donors on pulmonary and extrapulmonary acute respiratory distress syndrome.
  
  
  METHODS
  Prospective, randomized, controlled experimental study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Two hundred and twenty-five C57BL/6 mice.
  
  
  METHODS
  Acute respiratory distress syndrome was induced by Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). Control mice (Healthy) received saline solution intratracheally (Cp) or intraperitoneally (Cexp). After 24 hours, whole bone marrow cells were analyzed in vitro: 1) colony-forming unit-fibroblasts and 2) hematopoietic stem cells, neutrophils, T helper lymphocytes, B lymphocytes, and nonhematopoietic precursors. After cell characterization, all groups received saline or bone marrow-derived mononuclear cells (2 × 10), obtained from Cp, Cexp, ARDSp, and ARDSexp donor mice, IV, on day 1.
  
  
  RESULTS
  On day 1, in ARDSp, different patterns of colony formation were found, with nonstromal cells (mainly neutrophils) predominating over fibroblastoid colonies. In ARDSexp, irregular colony-forming unit-fibroblasts morphology with dispersed proliferating colonies and a greater number of hematopoietic stem cells were observed. In ARDSp, colony-forming unit-fibroblasts count was higher but not measurable in ARDSexp. In ARDSp, monocytes and T lymphocytes were increased and hematopoietic precursor cells reduced, with no significant changes in ARDSexp. On day 7, bone marrow-derived mononuclear cells improved survival and attenuated changes in lung mechanics, alveolar collapse, inflammation, pulmonary fibrosis, and apoptosis in the lung and distal organs, regardless of donor type.
  
  
  CONCLUSIONS
  Bone marrow-derived mononuclear cells from ARDSp and ARDSexp donors showed different characteristics but were as effective as cells obtained from healthy donors in reducing inflammation and remodeling, suggesting the utility of autologous transplant of bone marrow-derived mononuclear cells in the clinical setting.
authors.affiliation: 1Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 2Laboratory of Cellular and Molecular Cardiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 3Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho, Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 4Department of Radiology, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 5Laboratory of Immunopharmacology, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. 6Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil. 7Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
authors.forename: Johnatas D
authors.initials: JD
authors.lastname: Silva
authors.forename: Bruno D
authors.initials: BD
authors.lastname: Paredes
authors.forename: Indianara M
authors.initials: IM
authors.lastname: Araújo
authors.forename: Miquéias
authors.initials: M
authors.lastname: Lopes-Pacheco
authors.forename: Milena V
authors.initials: MV
authors.lastname: Oliveira
authors.forename: Grazielle D
authors.initials: GD
authors.lastname: Suhett
authors.forename: Lanuza A P
authors.initials: LA
authors.lastname: Faccioli
authors.forename: Edson
authors.initials: E
authors.lastname: Assis
authors.forename: Hugo C
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.forename: Regina C S
authors.initials: RC
authors.lastname: Goldenberg
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Débora G
authors.initials: DG
authors.lastname: Xisto
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D005260:Female; D005347:Fibroblasts; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D015656:Respiratory Mechanics; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D008070:Lipopolysaccharides