Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands.
Unit of Interstitial Lung Diseases, Pulmonary Department, University Hospital of Bellvitge, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
PLoS One. 2021 Mar 17;16(3):e0248415. doi: 10.1371/journal.pone.0248415. eCollection 2021.
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with limited treatment options in which the telomere shortening is a strong predictive factor of poor prognosis. Mesenchymal stromal cells (MSC) administration is probed in several experimental induced lung pathologies; however, MSC might stimulate fibrotic processes. A therapy that avoids MSC side effects of transformation would be an alternative to the use of living cells. Membranes particles (MP) are nanovesicles artificially generated from the membranes of MSC containing active enzymes involved in ECM regeneration. We aimed to investigate the anti-fibrotic role of MP derived from MSC in an in vitro model of pulmonary fibrosis.
Epithelial cells (A549) and lung fibroblasts, from IPF patients with different telomere length, were co-cultured with MP and TGF-β for 48h and gene expression of major pro-fibrotic markers were analyzed.
About 90% of both types of cells effectively took up MP without cytotoxic effects. MP decreased the expression of profibrotic proteins such as Col1A1, Fibronectin and PAI-1, in A549 cells. In fibroblasts culture, there was a different response in the inhibitory effect of MP on some pro-fibrotic markers when comparing fibroblast from normal telomere length patients (FN) versus short telomere length (FS), but both types showed an inhibition of Col1A1, Tenascin-c, PAI-1 and MMP-1 gene expression after MP treatment.
MP conserve some of the properties attributed to the living MSC. This study shows that MP target lung cells, via which they may have a broad anti-fibrotic effect.
特发性肺纤维化（IPF）是一种破坏性肺病，治疗选择有限，端粒缩短是预后不良的强预测因素。间充质基质细胞（MSC）在几种实验性诱导的肺病理学中被研究；然而，MSC 可能会刺激纤维化过程。避免 MSC 转化副作用的治疗方法将是替代活细胞的一种选择。膜颗粒（MP）是从 MSC 膜中人工产生的纳米囊泡，其中含有参与 ECM 再生的活性酶。我们旨在研究来自 MSC 的 MP 在体外肺纤维化模型中的抗纤维化作用。
上皮细胞（A549）和来自不同端粒长度的 IPF 患者的肺成纤维细胞与 MP 和 TGF-β 共培养 48 小时，分析主要促纤维化标志物的基因表达。
大约 90%的两种类型的细胞都能有效地摄取 MP，而没有细胞毒性作用。MP 降低了 A549 细胞中 Col1A1、纤维连接蛋白和 PAI-1 等促纤维化蛋白的表达。在成纤维细胞培养中，当比较正常端粒长度患者（FN）与短端粒长度患者（FS）的成纤维细胞时，MP 对某些促纤维化标志物的抑制作用存在不同的反应，但两种类型的细胞在 MP 处理后均表现出 Col1A1、Tenascin-c、PAI-1 和 MMP-1 基因表达的抑制。
MP 保留了一些归因于活 MSC 的特性。本研究表明，MP 靶向肺细胞，通过它们可能具有广泛的抗纤维化作用。
