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Late rescue therapy with cord-derived mesenchymal stromal cells for established lung injury in experimental bronchopulmonary dysplasia.

脐带间充质基质细胞晚期挽救治疗实验性支气管肺发育不良的肺损伤。

  • 影响因子:3.30
  • DOI:10.1089/scd.2019.0116
  • 作者列表:"O'Reilly M","Möbius MA","Vadivel A","Ionescu L","Fung M","Eaton F","Greer JJ","Thébaud B
  • 发表时间:2020-01-09
Abstract

:Bronchopulmonary dysplasia (BPD), the main complication of extreme prematurity, has life-long consequences for lung health. Mesenchymal stromal cells (MSC) prevent lung injury in experimental BPD in newborn rodents when given in the immediate neonatal period. Whether MSC therapy can restore normal lung growth after established lung injury in adulthood is clinically relevant, but currently unknown. Experimental BPD was achieved by exposing newborn rats to 95% O2 from postnatal days 4-14. Human umbilical cord-derived MSCs were intratracheally administered to rats (1x106cells/kg body weight) as a single dose at 3 or 6 months of age followed by assessment at 5 or 8 months of age, respectively. Lung alveolar structure and vessel density were histologically analyzed. O2-exposed rats exhibited persistent lung injury characterized by arrested alveolar growth with airspace enlargement and a lower vessel density at both 5 and 8 months of age compared to controls. Single-dose MSC treatment at 3 months partially attenuated O2-induced alveolar injury and restored vessel density at 5 months. Treatment with a single dose at 6 months did not attenuate alveolar injury or vessel density at 8 months. However, treatment with multiple MSC doses at 6, 6.5, 7, and 7.5 months significantly attenuated alveolar injury and improved vessel density at 8 months of age. Treatment of the adult BPD lung with MSCs has the potential to improve lung injury if administered in multiple doses or at an early stage of adulthood.

摘要

: 支气管肺发育不良 (BPD) 是极度早产的主要并发症,对肺部健康有终身影响。间充质基质细胞 (MSC) 在新生儿期给药时可防止新生啮齿类动物实验性 BPD 的肺损伤。MSC 治疗是否能在成年期建立肺损伤后恢复正常的肺生长是临床相关的,但目前尚不清楚。实验 BPD 是通过将新生大鼠暴露于出生后 4-14 天的 95% O2 来实现的。人脐带来源的 MSCs 在 3 或 6 月龄时以单次剂量气管内给予大鼠 (1x106cells/kg 体重),然后在 5 或 8 月龄时分别进行评估。对肺泡结构和血管密度进行组织学分析。与对照组相比,O2-暴露的大鼠表现出以肺泡生长停滞、空域扩大和 5 月龄和 8 月龄血管密度较低为特征的持续性肺损伤。3 个月时单剂量 MSC 治疗可部分减轻 O2-诱导的肺泡损伤,并在 5 个月时恢复血管密度。6 个月时单剂量治疗未减轻 8 个月时的肺泡损伤或血管密度。然而,在 6 、 6.5 、 7 和 7.5 个月时给予多次 MSC 治疗可显著减轻肺泡损伤,并在 8 个月时改善血管密度。用 MSCs 治疗成人 BPD 肺,如果多次给药或在成年早期阶段,有可能改善肺损伤。

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DOI:10.1007/s00464-019-07334-4
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影响因子:3.31
发表时间:2020-01-02
DOI:10.1007/s10916-019-1481-4
作者列表:["Matava, Clyde","Pankiv, Evelina","Raisbeck, Sam","Caldeira, Monica","Alam, Fahad"]

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影响因子:3.84
发表时间:2020-01-01
来源期刊:Chest
DOI:10.1016/j.chest.2019.06.018
作者列表:["Dhooria S","Chaudhary S","Ram B","Sehgal IS","Muthu V","Prasad KT","Aggarwal AN","Agarwal R"]

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