Department of Pediatrics/Division of Neonatology, University of Miami Miller School of Medicine, Miami, FL, USA.
Pediatr Res. 2013 Jan;73(1):46-53. doi: 10.1038/pr.2012.152. Epub 2012 Nov 8.
Mesenchymal stem cell (MSC) therapy may prevent neonatal hyperoxia-induced lung injury (HILI). There are, however, no clear data on the therapeutic efficacy of MSC therapy in established HILI, the duration of the reparative effects, and the exact mechanisms of repair. The main objective of this study was to evaluate whether the long-term reparative effects of a single intratracheal (IT) dose of MSCs or MSC-conditioned medium (CM) are comparable in established HILI.
Newborn rats exposed to normoxia or hyperoxia from postnatal day (P)2)-P16 were randomized to receive IT MSCs, IT CM, or IT placebo (PL) on P9. Alveolarization and angiogenesis were evaluated at P16, P30, and P100.
At all time periods, there were marked improvements in alveolar and vascular development in hyperoxic pups treated with MSCs or CM as compared with PL. This was associated with decreased expression of inflammatory mediators and an upregulation of angiogenic factors. Of note, at P100, the improvements were more substantial with MSCs as compared with CM.
These data suggest that acute effects of MSC therapy in HILI are mainly paracrine mediated; however, optimum long-term improvement following HILI requires treatment with the MSCs themselves or potentially repetitive administration of CM.
间充质干细胞(MSC)疗法可能预防新生鼠高氧诱导的肺损伤(HILI)。然而,在已建立的 HILI 中,MSC 疗法的治疗效果、修复效果的持续时间以及确切的修复机制均缺乏明确的数据。本研究的主要目的是评估单次气管内(IT)给予 MSC 或 MSC 条件培养基(CM)的长期修复效果在已建立的 HILI 中是否相当。
出生后第 2 天(P2)-P16 期间暴露于常氧或高氧的新生大鼠在 P9 时随机接受 IT MSC、IT CM 或 IT 安慰剂(PL)。在 P16、P30 和 P100 评估肺泡化和血管生成。
与 PL 相比,在所有时间点,接受 MSC 或 CM 治疗的高氧暴露幼鼠的肺泡和血管发育均有明显改善。这与炎症介质表达减少和血管生成因子上调有关。值得注意的是,在 P100 时,MSC 治疗的改善程度明显优于 CM。
这些数据表明,HILI 中 MSC 治疗的急性效应主要是旁分泌介导的;然而,HILI 后需要 MSC 本身或潜在的 CM 重复给药才能获得最佳的长期改善。