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Mesenchymal stem/stromal cells stably transduced with an inhibitor of CC chemokine ligand 2 ameliorate bronchopulmonary dysplasia and pulmonary hypertension
Cytotherapy ( IF 3.7 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.jcyt.2020.01.009
Toshihiko Suzuki 1 , Yoshiaki Sato 2 , Hidenori Yamamoto 3 , Taichi Kato 3 , Yuma Kitase 1 , Kazuto Ueda 1 , Haruka Mimatsu 1 , Yuichiro Sugiyama 2 , Atsuto Onoda 4 , Shigeki Saito 5 , Yoshiyuki Takahashi 3 , Takayuki Nakayama 6 , Masahiro Hayakawa 2
Affiliation  

Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone.

中文翻译:

用 CC 趋化因子配体 2 抑制剂稳定转导的间充质干/基质细胞改善支气管肺发育不良和肺动脉高压

围产期支气管肺发育不良(BPD)被定义为早产儿因多种因素引起的肺损伤,导致严重的呼吸功能障碍和高死亡率。已证明施用间充质干/基质细胞 (MSC) 治疗/预防 BPD 具有一定的治疗效果。然而,MSCs 只能微弱地调节巨噬细胞功能,而巨噬细胞功能与 BPD 的发展密切相关。7ND-MSC 是用 7ND 转染的 MSC,7ND 是 CC 趋化因子配体 2 (CCL2) 的截短版本,可使用慢病毒载体促进巨噬细胞活化。在本研究中,我们在 BPD 大鼠模型中显示,7ND-MSC 给药,但不是单独的 MSCs,改善了肺组织体积密度和表面积评估的肺泡化受损,以及 BPD 引起的肺动脉重构和肺动脉高压。此外,7ND-MSCs,但不是单独的 MSCs,减少了 M1 巨噬细胞和肺组织中白细胞介素 6 和 CCL2 的信使 RNA 表达。因此,本研究显示了 7ND-MSCs 在 BPD 大鼠模型中的治疗效果,比单独使用 MSCs 更有效。
更新日期:2020-04-01
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