title: Repeated administration of bone marrow-derived cells prevents disease progression in experimental silicosis.
abstract: OBJECTIVE
  Bone marrow-derived cells (BMDCs) reduced mechanical and histologic changes in the lung in a murine model of silicosis, but these beneficial effects did not persist in the course of lung injury. We hypothesized that repeated administration of BMDCs may decrease lung inflammation and remodeling thus preventing disease progression.
  
  
  METHODS
  One hundred and two C57BL/6 mice were randomly divided into SIL (silica, 20 mg intratracheally [IT]) and control (C) groups (saline, IT). C and SIL groups were further randomized to receive BMDCs (2×10(6) cells) or saline IT 15 and 30 days after the start of the protocol.
  
  
  RESULTS
  By day 60, BMDCs had decreased the fractional area of granuloma and the number of polymorphonuclear cells, macrophages (total and M1 phenotype), apoptotic cells, the level of transforming growth factor (TGF)-β' and types I and III collagen fiber content in the granuloma. In the alveolar septa, BMDCs reduced the amount of collagen and elastic fibers, TGF-β, and the number of M1 and apoptotic cells. Furthermore, interleukin (IL)-1β, IL-1R1, caspase-3 mRNA levels decreased and the level of IL-1RN mRNA increased. Lung mechanics improved after BMDC therapy. The presence of male donor cells in lung tissue was not observed using detection of Y chromosome DNA.
  
  
  CONCLUSIONS
  repeated administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis, thus improving lung mechanics through the release of paracrine factors.
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Brazil.
authors.forename: Miquéias
authors.initials: M
authors.lastname: Lopes-Pacheco
authors.forename: Debora G
authors.initials: DG
authors.lastname: Xisto
authors.forename: Felipe M
authors.initials: FM
authors.lastname: Ornellas
authors.forename: Mariana A
authors.initials: MA
authors.lastname: Antunes
authors.forename: Soraia C
authors.initials: SC
authors.lastname: Abreu
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
authors.forename: Christina M
authors.initials: CM
authors.lastname: Takiya
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006099:Granuloma / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity; D012829:Silicosis / Q000209:etiology / Q000517:prevention & control* / Q000601:surgery
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D016207:Cytokines; D012333:RNA, Messenger; D012822:Silicon Dioxide; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9