Silicosis is an occupational respiratory disease caused by long-term excessive silica inhalation, which is most commonly encountered in industrial settings. Unfortunately, there is no effective therapy to delay and cure the progress of silicosis. In the recent years, stem cell therapy has emerged as an attractive tool against pulmonary fibrosis (PF) owing to its unique biological characteristics. However, the direct use of stem cells remains limitation by many risk factors for therapeutic purposes. The exclusive utility of exosomes secreted from stem cells, rather than cells, has been considered a promising alternative to overcome the limitations of cell-based therapy while maintaining its advantages. In this study, we first employed a three-dimensional (3D) dynamic system to culture human umbilical cord mesenchymal stem cell (hucMSC) spheroids in a microcarrier suspension to yield exosomes from serum-free media. Experimental silicosis was induced in C57BL/6J mice by intratracheal instillation of a silica suspension, with/without exosomes derived from hucMSC (hucMSC-Exos), injection via the tail vein afterwards. The results showed that the gene expression of collagen I (COL1A1) and fibronectin (FN) was upregulated in the silica group as compared to that in the control group; however, this change decreased with hucMSC-Exo treatment. The value of FEV0.1 decreased in the silica group as compared to that in the control group, and this change diminished with hucMSC-Exo treatment. These findings suggested that hucMSC-Exos could inhibit silica-induced PF and regulate pulmonary function. We also performed in vitro experiments to confirm these findings; the results revealed that hucMSC-Exos decreased collagen deposition in NIH-3T3 cells exposed to silica. Taken together, these studies support a potential role for hucMSC-Exos in ameliorating pulmonary fibrosis and provide new evidence for improving clinical treatment induced by silica.

中文翻译：

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三维培养的人脐带间充质干细胞来源的外泌体改善了小鼠矽肺病模型中的肺纤维化

矽肺病是由长期过量吸入二氧化硅引起的职业性呼吸系统疾病，在工业环境中最常见。不幸的是，没有有效的疗法来延迟和治愈矽肺病的进展。近年来，由于其独特的生物学特性，干细胞疗法已成为对抗肺纤维化（PF）的有吸引力的工具。然而，出于治疗目的，直接使用干细胞仍然受到许多危险因素的限制。从干细胞而非细胞中分泌出来的外泌体具有排他性的用途，被认为是克服基于细胞疗法的局限性并保持其优势的有前途的替代方法。在这个研究中，我们首先采用三维（3D）动力学系统在微载体悬浮液中培养人脐带间充质干细胞（hucMSC）球状体，以从无血清培养基中产生外泌体。通过气管内滴注二氧化硅悬浮液（含/不含衍生自hucMSC的外泌体（hucMSC-Exos）），然后经尾静脉注射，在C57BL / 6J小鼠中诱发实验性矽肺病。结果表明，与对照组相比，硅胶组胶原蛋白I（COL1A1）和纤连蛋白（FN）的基因表达上调。但是，这种变化随着hucMSC-Exo处理而减少。与对照组相比，硅胶组的FEV0.1值降低，并且通过hucMSC-Exo处理减少了这种变化。这些发现表明hucMSC-Exos可以抑制二氧化硅诱导的PF并调节肺功能。我们还进行了体外实验，以确认这些发现。结果表明，hucMSC-Exos减少了暴露于二氧化硅的NIH-3T3细胞中的胶原沉积。综上所述，这些研究支持hucMSC-Exos在改善肺纤维化方面的潜在作用，并为改善二氧化硅诱导的临床治疗提供了新的证据。