Engineered Fibroblast Extracellular Vesicles Attenuate Pulmonary Inflammation and Fibrosis in Bleomycin-Induced Lung Injury.
Engineered Fibroblast Extracellular Vesicles Attenuate Pulmonary Inflammation and Fibrosis in Bleomycin-Induced Lung Injury.
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工程化成纤维细胞胞外囊泡减轻博莱霉素诱导肺损伤的肺部炎症和纤维化。
DOI：
10.3389/fcell.2021.733158
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发表时间：
2021
影响因子：
5.5
通讯作者：
Ibrahim AG
中科院分区：
文献类型：
--
作者：
Ibrahim A;Ciullo A;Li C;Akhmerov A;Peck K;Jones-Ungerleider KC;Morris A;Marchevsky A;Marbàn E;Ibrahim AG
肺纤维化是一种进行性疾病，目前尚无治愈性治疗。我们以前已经设计了真皮成纤维细胞，以产生具有组织修复特性的细胞外囊泡，称为激活的专门组织效应细胞外囊泡（ASTEX）。在这里，我们研究了ASTEX在体外和博莱霉素诱导的肺损伤小鼠模型中的治疗效用。RNA测序表明，与来自未转导的真皮成纤维细胞EV（DF-EV）的EV相比，ASTEX富含微小RNA（miR）货物。与DF-EV暴露的巨噬细胞相比，用ASTEX处理原代巨噬细胞降低了白细胞介素（IL）6的表达，增加了IL 10的表达。此外，人肺成纤维细胞或血管内皮细胞暴露于ASTEX降低了平滑肌肌动蛋白的表达，平滑肌肌动蛋白是成肌纤维细胞分化的标志（分别）。在体内，在未经处理的健康小鼠中，ASTEX经皮给药表现出有利的安全性特征，在给药后3周，体重、肺重量/体重、纤维化负荷或组织学评分均无变化。在肺损伤的急性期（短期）博来霉素模型中，ASTEX降低了肺重量与体重的比值、IL 6表达和循环单核细胞。在长期环境中，ASTEX提高了生存率并减少了肺组织中的纤维化含量。这些结果表明ASTEX在肺损伤中具有潜在的免疫调节和抗纤维化特性。
Pulmonary fibrosis is a progressive disease for which no curative treatment exists. We have previously engineered dermal fibroblasts to produce extracellular vesicles with tissue reparative properties dubbed activated specialized tissue effector extracellular vesicles (ASTEX). Here, we investigate the therapeutic utility of ASTEX in vitro and in a mouse model of bleomycin-induced lung injury. RNA sequencing demonstrates that ASTEX are enriched in micro-RNAs (miRs) cargo compared with EVs from untransduced dermal fibroblast EVs (DF-EVs). Treating primary macrophages with ASTEX reduced interleukin (IL)6 expression and increased IL10 expression compared with DF-EV-exposed macrophages. Furthermore, exposure of human lung fibroblasts or vascular endothelial cells to ASTEX reduced expression of smooth muscle actin, a hallmark of myofibroblast differentiation (respectively). In vivo, intratracheal administration of ASTEX in naïve healthy mice demonstrated a favorable safety profile with no changes in body weight, lung weight to body weight, fibrotic burden, or histological score 3 weeks postexposure. In an acute phase (short-term) bleomycin model of lung injury, ASTEX reduced lung weight to body weight, IL6 expression, and circulating monocytes. In a long-term setting, ASTEX improved survival and reduced fibrotic content in lung tissue. These results suggest potential immunomodulatory and antifibrotic properties of ASTEX in lung injury.
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影响因子：
5.8
作者：
De Langhe E;Cailotto F;De Vooght V;Aznar-Lopez C;Vanoirbeek JA;Luyten FP;Lories RJ
通讯作者：
Lories RJ
DOI：
10.4049/jimmunol.1302470
发表时间：
2014-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Le TT;Karmouty-Quintana H;Melicoff E;Le TT;Weng T;Chen NY;Pedroza M;Zhou Y;Davies J;Philip K;Molina J;Luo F;George AT;Garcia-Morales LJ;Bunge RR;Bruckner BA;Loebe M;Seethamraju H;Agarwal SK;Blackburn MR
通讯作者：
Blackburn MR
影响因子：
5.6
作者：
Kendall RT;Feghali-Bostwick CA
通讯作者：
Feghali-Bostwick CA
影响因子：
168.9
作者：
Makkar, Raj R.;Smith, Rachel R.;Cheng, Ke;Malliaras, Konstantinos;Thomson, Louise E. J.;Berman, Daniel;Czer, Lawrence S. C.;Marban, Linda;Mendizabal, Adam;Johnston, Peter V.;Russell, Stuart D.;Schuleri, Karl H.;Lardo, Albert C.;Gerstenblith, Gary;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
28.1
作者：
Ibrahim, Ahmed G. E.;Li, Chang;Marban, Eduardo
通讯作者：
Marban, Eduardo