Lopes-Pacheco Miquéias, Ventura Túlio G, de Oliveira Helena D'Anunciação, Monção-Ribeiro Leonardo C, Gutfilen Bianca, de Souza Sergio A L, Rocco Patrícia R M, Borojevic Radovan, Morales Marcelo M, Takiya Christina M
Laboratory of Cellular Pathology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Cellular and Molecular Physiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Pulmonary Investigation, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratory of Cellular Pathology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
PLoS One. 2014 Oct 9;9(10):e109982. doi: 10.1371/journal.pone.0109982. eCollection 2014.
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.
我们假设，在二氧化硅诱导损伤的后期注入骨髓单个核细胞（BMMCs）会减少矽肺小鼠模型中的重塑过程。将C57BL/6小鼠分为2组。在SIL组中，小鼠经气管内滴注二氧化硅颗粒悬浮液。对照组（C）小鼠按照相同方案接受生理盐水。在第40天，两组中的一些动物被处死。其余动物静脉注射生理盐水或BMMCs（1×10⁶个细胞）（C+BMMC组和SIL+BMMC组），并在方案开始70天后处死小鼠。在SIL+BMMC组小鼠中，胶原沉积、结节内二氧化硅颗粒的存在、巨噬细胞的存在以及对诱导型一氧化氮合酶有反应的细胞均减少。肺参数也有所改善。除此之外，支气管肺泡灌洗液的总细胞数和分类细胞数、转化生长因子-β的免疫表达、调节性T细胞的数量以及细胞凋亡均增加。然而，使用绿色荧光蛋白阳性细胞（40天）或Y染色体DNA（70天）未在肺组织中观察到雄性供体细胞的存在。因此，实验性矽肺后期的BMMC治疗通过减少纤维化改善了肺功能，但炎性细胞持续存在，这可能与调节性T细胞的扩增有关，调节性T细胞负责细胞治疗的有益效果。
