The Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
Pediatr Res. 2017 Dec;82(6):1030-1038. doi: 10.1038/pr.2017.170. Epub 2017 Aug 16.
BACKGROUNDWhite matter brain injury in preterm infants can induce neurodevelopmental deficits. Umbilical cord blood (UCB) cells demonstrate neuroprotective properties, but it is unknown whether cells obtained from preterm cord blood (PCB) vs. term cord blood (TCB) have similar efficacy. This study compared the ability of TCB vs. PCB cells to reduce white matter injury in preterm fetal sheep.METHODSHypoxia-ischemia (HI) was induced in fetal sheep (0.7 gestation) by 25 min umbilical cord occlusion. Allogeneic UCB cells from term or preterm sheep, or saline, were administered to the fetus at 12 h after HI. The fetal brain was collected at 10-day post HI for assessment of white matter neuropathology.RESULTSHI (n=7) induced cell death and microglial activation and reduced total oligodendrocytes and CNPase+myelin protein in the periventricular white matter and internal capsule when compared with control (n=10). Administration of TCB or PCB cells normalized white matter density and reduced cell death and microgliosis (P<0.05). PCB prevented upregulation of plasma tumor necrosis factor (TNF)-a, whereas TCB increased anti-inflammatory interleukin (IL)-10 (P<0.05). TCB, but not PCB, reduced circulating oxidative stress.CONCLUSIONSTCB and PCB cells reduced preterm HI-induced white matter injury, primarily via anti-inflammatory actions. The secondary mechanisms of neuroprotection appear different following TCB vs. PCB administration.
早产儿的脑白质损伤可导致神经发育缺陷。脐带血(UCB)细胞具有神经保护作用,但尚不清楚早产儿脐带血(PCB)与足月脐带血(TCB)来源的细胞是否具有相似的疗效。本研究比较了 TCB 与 PCB 细胞减少早产胎羊脑白质损伤的能力。
通过 25 分钟脐带结扎使 0.7 孕期的胎羊发生缺氧缺血(HI)。HI 后 12 小时,将来自足月或早产羊的同种异体 UCB 细胞或生理盐水给予胎儿。HI 后 10 天收集胎脑,评估白质神经病理学。
HI(n=7)与对照组(n=10)相比,诱导了细胞死亡和小胶质细胞激活,并减少了脑室周围白质和内囊中的总少突胶质细胞和 CNPase+髓鞘蛋白。给予 TCB 或 PCB 细胞可使白质密度正常化,并减少细胞死亡和小胶质细胞增生(P<0.05)。PCB 可预防血浆肿瘤坏死因子(TNF)-a 的上调,而 TCB 则增加抗炎性白细胞介素(IL)-10(P<0.05)。TCB 而非 PCB 可减少循环氧化应激。
TCB 和 PCB 细胞减少了早产 HI 诱导的白质损伤,主要通过抗炎作用。TCB 与 PCB 给药后的神经保护的次要机制不同。