Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan.
Stem Cell Res Ther. 2021 May 1;12(1):258. doi: 10.1186/s13287-021-02335-4.
Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated hyperoxia-induced lung injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on hyperoxia-induced lung injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on hyperoxia-induced lung injury.
Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O received intratracheal NS or hUC-MSCs (3 × 10 or 3 × 10 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O + NS + NS, O + surfactant + NS, O + surfactant + hUC-MSCs (3 × 10 cells), and O + surfactant + hUC-MSCs (3 × 10 cells). The lungs were excised for histological, western blot, and cytokine analyses.
The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1β and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 10 cells) treatment attenuated hyperoxia-induced lung injury. The surfactant + hUC-MSCs (3 × 10 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 10 cells) group did.
Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating hyperoxia-induced lung injury in neonates.
表面活性剂治疗是治疗呼吸窘迫早产儿的标准治疗方法，可降低这些患者的死亡率和支气管肺发育不良的发生率。我们之前的研究发现，间充质干细胞（MSCs）可减轻高氧诱导的肺损伤，并且表面活性剂和人脐带间充质干细胞（hUC-MSCs）联合治疗对新生大鼠高氧诱导的肺损伤没有相加作用。目的是评估连续两天经气管内给予表面活性剂和 hUC-MSCs 对高氧诱导的肺损伤的影响。
新生 Sprague Dawley 大鼠在生后第 1 天至第 14 天分别在空气（RA）或高氧（85% O）中饲养。在生后第 4 天，大鼠接受气管内注射 20μL 生理盐水（NS）或 20μL 表面活性剂。在生后第 5 天，RA 饲养的大鼠接受气管内 NS，O 饲养的大鼠接受气管内 NS 或 hUC-MSCs（3×10 或 3×10 个细胞）。共检查 6 个研究组：RA+NS+NS、RA+surfactant+NS、O+NS+NS、O+surfactant+NS、O+surfactant+hUC-MSCs（3×10 个细胞）和 O+surfactant+hUC-MSCs（3×10 个细胞）。取出肺组织进行组织学、western blot 和细胞因子分析。
在高氧中饲养并接受 NS 处理的大鼠的平均线性截距（MLIs）和白细胞介素（IL）-1β和 IL-6 水平显著升高，而血管内皮生长因子（VEGFs）、血小板衍生生长因子蛋白表达和血管密度显著降低，而在 RA 中饲养并接受 NS 或表面活性剂处理的大鼠则不然。较低的 MLIs 和细胞因子以及较高的 VEGF 表达和血管密度表明，表面活性剂和表面活性剂+hUC-MSCs（3×10 个细胞）治疗可减轻高氧诱导的肺损伤。与表面活性剂+hUC-MSCs（3×10 个细胞）组相比，表面活性剂+hUC-MSCs（3×10 个细胞）组的 MLI 显著降低，VEGF 表达和血管密度显著升高。
连续每日经气管内给予表面活性剂和 hUC-MSCs 可作为治疗新生儿高氧诱导肺损伤的有效方案。
