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Repeated Administration of Bone Marrow-Derived Cells Prevents Disease Progression in Experimental Silicosis

机译:重复施用骨髓衍生细胞可预防实验性矽肺病的疾病进展

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biBackground/Aims /i/bBone 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. biMethods /i/bOne 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 (2×10sup6/sup cells) or saline IT 15 and 30 days after the start of the protocol. biResults /i/bBy 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. biConclusion /i/brepeated administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis, thus improving lung mechanics through the release of paracrine factors.
机译:背景/目标 在矽肺小鼠模型中,骨髓来源的细胞(BMDC)减少了肺部的机械和组织学变化,但这些有益作用并未持续肺损伤。我们假设重复给药BMDC可以减少肺部炎症和重塑,从而预防疾病进展。 方法 将120只C57BL / 6小鼠随机分为SIL组(硅胶,气管内[IT] 20 mg)和对照组(C)(盐水,IT)。方案开始后15天和30天,C组和SIL组进一步随机分配接受BMDC(2×10 6 细胞)或生理盐水。 结果 到第60天,BMDC减少了肉芽肿的面积和多形核细胞,巨噬细胞(总表型和M1型),凋亡细胞,转化生长水平因子(TGF)-β?肉芽肿中的I型和III型胶原纤维含量。在肺泡隔中,BMDC减少了胶原蛋白和弹性纤维,TGF-β的数量以及M1和凋亡细胞的数量。此外,白介素(IL)-1β,IL-1R1,caspase-3 mRNA水平降低,IL-1RN mRNA水平升高。 BMDC治疗后,肺力学得以改善。使用Y染色体DNA检测未观察到肺组织中雄性供体细胞的存在。 结论 重复施用BMDC可以减少炎症,纤维发生和弹性生成,从而通过释放旁分泌因子来改善肺部力学。

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