Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Stem Cell Res Ther. 2017 Nov 10;8(1):259. doi: 10.1186/s13287-017-0699-7.
Administration of bone marrow mononuclear cells (BMMCs) modulates lung inflammation and fibrosis in experimental silicosis. However, no studies have evaluated whether silicosis affects the efficacy of autologous BMMCs treatment. We hypothesized that BMMCs obtained from healthy or silicotic mice may improve lung function, but they might affect the inflammatory and fibrotic processes differently in experimental silicosis.
C57BL/6 mice were randomly divided into control (C) and silicosis (SIL) groups. Mice in the SIL group were instilled with silica particles intratracheally; the C animals received saline using the same protocol. On day 15, the animals were treated with saline (Sal) or BMMCs (2 × 10 cells) from healthy (BMMC-healthy) and silicotic (BMMC-sil) donors. Lung mechanics were measured, and lungs were collected for histology and molecular biology analysis.
BMMCs obtained from healthy and silicotic donors presented similar percentages of cell populations. Tc-BMMCs tracking revealed preferential migration of cells to the liver, and only a few GFP BMMCs were observed in lung tissue 24 h after treatment, regardless of donor type. Both the SIL-BMMC-healthy and SIL-BMMC-sil groups showed improvement in lung function, a reduction in the fractional area of granuloma, and a decrease in the number of mononuclear and apoptotic cells in lung parenchyma. In addition, the number of F4/80 macrophages, the levels of interleukin-1 beta and transforming growth factor beta, and collagen fiber content in granuloma were reduced in SIL-BMMC-healthy mice, whereas mRNA expression of MMP-9 and procollagen I and III was reduced in the SIL-BMMC-sil group.
Administration of BMMCs from healthy and silicotic donors reduced lung inflammation and fibrosis, thus improving lung function. In addition, BMMC-healthy exhibited a greater improvement in lung morpho-functional changes in murine model of silicosis.
骨髓单核细胞（BMMC）的给药可调节实验性矽肺中的肺炎症和纤维化。然而，尚无研究评估矽肺是否会影响自体 BMMC 治疗的效果。我们假设，来自健康或矽肺小鼠的 BMMC 可能会改善肺功能，但它们可能会以不同的方式影响实验性矽肺中的炎症和纤维化过程。
将 C57BL/6 小鼠随机分为对照组（C）和矽肺组（SIL）。SIL 组的小鼠通过气管内滴注二氧化硅颗粒；C 组的动物则采用相同方案接受生理盐水处理。在第 15 天，用生理盐水（Sal）或来自健康（BMMC-healthy）和矽肺（BMMC-sil）供体的 BMMC（2×10 个细胞）处理动物。测量肺力学，并收集肺组织进行组织学和分子生物学分析。
来自健康和矽肺供体的 BMMC 具有相似的细胞群体百分比。Tc-BMMC 示踪显示细胞优先迁移到肝脏，并且无论供体类型如何，在治疗后 24 小时，仅观察到少量 GFP-BMMC 存在于肺组织中。SIL-BMMC-healthy 和 SIL-BMMC-sil 组的肺功能均得到改善，肉芽肿的分形面积减小，肺实质中单核细胞和凋亡细胞的数量减少。此外，SIL-BMMC-healthy 组的 F4/80 巨噬细胞数量、白细胞介素 1β和转化生长因子-β水平以及肉芽肿中的胶原纤维含量降低，而 SIL-BMMC-sil 组的 MMP-9 和前胶原 I 和 III 的 mRNA 表达降低。
给予来自健康和矽肺供体的 BMMC 可减少肺炎症和纤维化，从而改善肺功能。此外，BMMC-healthy 在矽肺小鼠模型中对肺形态功能变化的改善更为明显。
