Infusion of bone marrow mononuclear cells reduces lung fibrosis but not inflammation in the late stages of murine silicosis.

Abstract

We hypothesized that infusion of bone marrow mononuclear cells (BMMCs) in the late stages of silica-induced damage would reduce the remodelling process in a murine model of silicosis. C57BL/6 mice were assigned to 2 groups. In the SIL group, mice were instilled with a silica particle suspension intratracheally. Control (C) mice received saline under the same protocol. On the 40th day, some of the animals from both groups were killed. The others were treated with either saline or BMMCs (1×10(6) cells) intravenously (C+BMMC and SIL+BMMC), and the mice were killed 70 days after the start of the protocol. In the mice in the SIL+BMMC group, collagen deposition, the presence of silica particles inside nodules, the presence of macrophages and cells reactive for inducible nitric oxide synthase were reduced. Lung parameters also improved. Beyond that, the total and differential cellularity of bronchoalveolar lavage fluid, immunoexpression of transforming growth factor-β, the number of T regulatory cells and apoptosis were increased. However, the presence of male donor cells in lung tissue was not observed using GFP+ cells (40d) or Y chromosome DNA (70d). Therefore, BMMC therapy in the late stages of experimental silicosis improved lung function by diminishing fibrosis but inflammatory cells persisted, which could be related to expansion of T regulatory cells, responsible for the beneficial effects of cell therapy.

• Authors: Miquéias Lopes-Pacheco, Túlio G Ventura, Helena D'Anunciação de Oliveira, Leonardo C Monção-Ribeiro, Bianca Gutfilen, Sergio A L de Souza, Patrícia R M Rocco, Radovan Borojevic, Marcelo M Morales, Christina M Takiya
• Journal: PloS one (PLoS One) Vol. 9 Issue 10 Pg. e109982 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25299237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Silicon Dioxide

Topics

• Animals
• Apoptosis (genetics)
• Bone Marrow Transplantation
• Cell- and Tissue-Based Therapy
• Disease Models, Animal
• Inflammation (chemically induced, pathology, therapy)
• Leukocytes, Mononuclear (cytology, transplantation)
• Mice
• Pulmonary Fibrosis (chemically induced, pathology, therapy)
• Silicon Dioxide (toxicity)
• Silicosis (pathology, therapy)