Department of Anatomy and Cellular Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan.
Pediatr Neonatol. 2020 Oct;61(5):498-505. doi: 10.1016/j.pedneo.2020.05.012. Epub 2020 Jun 3.
Hyperoxia increases Sonic hedgehog (Shh) expression in neonatal rat lungs. The effect of mesenchymal stem cells (MSCs) on the hedgehog signaling pathway in hyperoxia-induced lung injury is unknown. This study evaluated whether MSCs could inhibit hedgehog signaling and improve established hyperoxia-induced lung injury in newborn rats.
Newborn rats were assigned to room air (RA) or hyperoxia (85% O) groups from postnatal day 4-15, and some received intravenous injection of human MSCs (9 × 10 cells) in 90 μL of normal saline (NS) through the tail vein on postnatal day 15. We obtained four study groups as follows: RA + NS, RA + MSCs, O + NS, and O + MSCs. Pups from each group were sacrificed on postnatal days 15 and 29, and lungs were removed for histological and Western blot analyses.
Neonatal hyperoxia on postnatal days 4-15 reduced the body weight, increased the mean linear intercept, and decreased the vascular density of the rats, and these effects were associated with increased Shh and Smoothened (Smo) expression and decreased Patched expression. By contrast, the MSC-treated hyperoxic pups exhibited improved alveolarization, increased vascularization, and decreased Shh and Smo expression on postnatal day 29.
Human MSC treatment reversed established hyperoxia-induced lung injury in newborn rats, probably through suppression of the hedgehog pathway.
高氧可增加新生鼠肺中的 Sonic hedgehog（Shh）表达。间充质干细胞（MSCs）对高氧诱导肺损伤中 hedgehog 信号通路的影响尚不清楚。本研究评估了 MSCs 是否可以抑制 hedgehog 信号通路并改善新生大鼠已建立的高氧诱导肺损伤。
新生大鼠于生后 4-15 天分别被分配至空气（RA）或高氧（85% O）组，并于生后 15 天经尾静脉给予 90 μL 生理盐水（NS）中的 9×10 个细胞的人 MSCs 静脉注射。我们获得了四个研究组，分别为 RA+NS、RA+MSCs、O+NS 和 O+MSCs。每组的幼鼠于生后 15 天和 29 天处死，取肺组织进行组织学和 Western blot 分析。
生后 4-15 天的新生大鼠高氧降低了体重，增加了平均线性截距，并降低了大鼠的血管密度，这些影响与 Shh 和 Smoothened（Smo）表达增加以及 Patched 表达减少有关。相比之下，MSCs 治疗的高氧幼鼠在生后 29 天表现出肺泡化改善、血管化增加以及 Shh 和 Smo 表达减少。
人 MSC 治疗逆转了新生大鼠已建立的高氧诱导肺损伤，可能是通过抑制 hedgehog 通路。
