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Inhalational delivery of induced pluripotent stem cell secretome improves postpneumonectomy lung structure and function.
Journal of Applied Physiology ( IF 3.3 ) Pub Date : 2020-09-10 , DOI: 10.1152/japplphysiol.00205.2020
D Merrill Dane 1 , Khoa Cao 1 , Yu-An Zhang 1 , Kemp H Kernstine 2 , Amiq Gazdhar 3, 4 , Thomas Geiser 3, 4 , Connie C W Hsia 1
Affiliation  

Cell-free secretory products (secretome) of human induced pluripotent stem cells (iPSCs) have been shown to attenuate tissue injury and facilitate repair and recovery. To examine whether iPSC secretome facilitates mechanically-induced compensatory responses following unilateral pneumonectomy (PNX), litter-matched young adult female hounds underwent right PNX (removing 55-58% of lung units) followed by inhalational delivery of either the nebulized conditioned media containing iPSCs secretome (iPSC CM) or control cell-free media (CFM); inhalation was repeated every 5 days for 10 treatments. Lung function was measured under anesthesia pre-PNX and 10 d after the last treatment (8 weeks post-PNX); detailed quantitative analysis of lung ultrastructure was performed postmortem. Pre-PNX lung function was similar between groups. Compared to CFM control, treatment with iPSC CM attenuated the post-PNX decline in DLCO and DMCO, accompanied by a 24% larger postmortem lobar volume and distal air space enlargement. Alveolar double-capillary profiles were 39% more prevalent consistent with enhanced intussusceptive angiogenesis. Frequency distribution of the harmonic mean thickness of alveolar blood-gas barrier shifted towards the lowest values while alveolar septal tissue volume and arithmetic septal thickness were similar, indicating septal remodeling and reduced diffusive resistance of the blood-gas barrier. Thus, repetitive inhalational delivery of iPSC secretome enhanced post-PNX alveolar angiogenesis and septal remodeling that are associated with improved gas exchange compensation. Results highlight the plasticity of the remaining lung units following major loss of lung mass that are responsive to broad-based modulation provided by the iPSC secretome.

中文翻译:

诱导多能干细胞分泌组的吸入递送可改善肺切除术后肺结构和功能。

人类诱导多能干细胞 (iPSCs) 的无细胞分泌产物 (secretome) 已被证明可以减轻组织损伤并促进修复和恢复。为了检查 iPSC 分泌组是否促进单侧肺切除术 (PNX) 后机械诱导的补偿反应,同窝的年轻成年雌性猎犬接受右侧 PNX(去除 55-58% 的肺单位),然后吸入递送含有 iPSC 的雾化条件培养基分泌组 (iPSC CM) 或对照无细胞培养基 (CFM);每 5 天重复吸入一次,共 10 个治疗。在麻醉前 PNX 和最后一次治疗后 10 天(PNX 后 8 周)测量肺功能;死后对肺超微结构进行了详细的定量分析。组间 PNX 前肺功能相似。与 CFM 控制相比,CO和DM CO,伴随着死后 24% 的大叶体积和远端气腔扩大。肺泡双毛细血管分布与增强的肠套叠血管生成一致,多出 39%。肺泡血气屏障调和平均厚度的频率分布向最低值移动,而肺泡间隔组织体积和算术间隔厚度相似,表明间隔重塑和血气屏障扩散阻力降低。因此,iPSC 分泌组的重复吸入递送增强了 PNX 后肺泡血管生成和间隔重塑,这与改善的气体交换补偿相关。结果突出了肺质量的主要损失后剩余肺单位的可塑性,这些肺质量对 iPSC 分泌组提供的广泛调节有反应。
更新日期:2020-09-11
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