Chicha L, Smith T, Guzman R
Department of Biomedicine, University of Basel, Basel, Switzerland.
Childs Nerv Syst. 2014 Jan;30(1):37-46. doi: 10.1007/s00381-013-2304-4. Epub 2013 Nov 1.
Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.
新生儿缺氧缺血性损伤是小儿脑病、发育迟缓及痉挛性脑瘫的重要病因。尽管发育中的大脑具有可塑性,能够实现显著的自我修复,但新生儿脑损伤后正常髓鞘形成和皮质发育的严重破坏,很可能在成长中的儿童身上产生持续终生的感觉运动和认知缺陷。目前,尚无能够解决这些长期后果的治疗方法。因此,再生医学似乎是一条有望帮助受影响婴儿恢复正常发育过程的途径。干细胞疗法已在新生儿缺氧缺血性损伤的动物模型中被证明能有效促进功能恢复,因此是针对这种未满足医疗需求的一种有希望的治疗方法。源自多能干细胞或胎儿组织的神经干细胞以及脐带血和间充质干细胞,在改善功能结局方面均已初显成效。然而,关于如何将这些干细胞安全地应用于婴儿以及它们在大脑中的修复机制仍有许多有待了解之处。在本综述中,我们讨论了关于新生儿脑损伤病理生理机制的最新研究、目前在此背景下正在测试的干细胞疗法类型,以及外源性干细胞可能与发育中的大脑相互作用并产生影响的潜在机制。