The Ritchie Centre, MIMR-PHI Institute , Clayton, VIC , Australia.
The Ritchie Centre, MIMR-PHI Institute , Clayton, VIC , Australia ; Department of Paediatrics, Monash University , Clayton, VIC , Australia.
Front Neurol. 2014 Oct 9;5:200. doi: 10.3389/fneur.2014.00200. eCollection 2014.
Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP). Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB) contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia-ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia-ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB-derived from preterm and term infants for use in clinical applications.
新生儿护理的重大进展导致早产儿的存活率显著提高,但这是有代价的,早产与神经功能缺陷(包括脑瘫)之间存在着强有力的因果关系。事实上,在高收入国家,多达 50%的脑瘫儿童是早产儿。将早产与脑损伤联系起来的途径是复杂的、多因素的,但很明显,早产与发育中大脑的白质损伤密切相关。近 90%以后发展为痉挛性脑瘫的早产儿都有脑室周围白质损伤的证据。目前还没有针对保护未成熟早产儿大脑的治疗方法。脐带血(UCB)含有多种干细胞和祖细胞,由于其在伦理和实际方面相对于其他潜在治疗性细胞类型的优势,是临床应用中一种特别有前途的细胞来源。最近的研究记录了 UCB 细胞在减少脑损伤方面的潜在益处,特别是在足月新生儿缺氧缺血的啮齿动物模型中。这些研究表明,UCB 细胞通过抗炎和免疫调节作用发挥作用,并释放神经营养生长因子来支持受损和周围的脑组织。早产儿脑损伤的病因不如足月婴儿那么清楚,但可能是由于发育期白质脆弱期间发生的灌注不足、缺氧缺血和/或炎症发作所致。这篇综述将探讨关于 UCB 细胞的神经保护作用的现有知识,以及通过新生儿细胞给药来改善早产儿脑损伤的潜力。我们还将讨论来自早产儿和足月婴儿的 UCB 用于临床应用的特征。