Instituto de Ciências Biomédicas, Instituto de Biofísica Carlos Chagas Filho and Programa de Terapia Celular, UFRJ, Rio de Janeiro, Brazil.
Stem Cells Dev. 2010 Mar;19(3):299-310. doi: 10.1089/scd.2009.0403.
Neonatal hypoxic-ischemic encephalopathy (HIE) is a common cause of long-term neurological disability in children. Despite advances in supportive care, no treatments for HIE are available at present. The potential use of stem/progenitor cell therapies for neuroprotection or regeneration of the damaged adult brain has been evaluated in several preclinical studies, and the most promising results are now being tested in clinical trials. In recent years, the use of stem/progenitor cell transplantation in animal models of HIE has also been evaluated in several laboratories. It was shown that human umbilical cord blood mononuclear cells and mesenchymal stem/progenitor cells may have a therapeutic potential through multiple mechanisms acting locally in the central nervous system and possibly in peripheral organs of hypoxic-ischemic animals. Neural stem/progenitor cells (NSCs) have also been transplanted in animal models of HIE, migrating long distances to ischemic brain areas and differentiating into neurons. The results of these studies have raised important questions that must be addressed before these findings can be translated to the bedside. In this review, we give a critical overview of the different studies published up to now, and we discuss the endogenous regenerative potential of NSCs of the newborn brain when challenged by an HIE insult. We also discuss the use of cell therapies for the encephalopathy of prematurity.
新生儿缺氧缺血性脑病(HIE)是儿童长期神经功能障碍的常见原因。尽管支持性治疗取得了进展,但目前尚无 HIE 的治疗方法。在几项临床前研究中,评估了干细胞/祖细胞疗法在保护受损成年大脑或促进其再生方面的潜在用途,最有前途的结果正在临床试验中进行测试。近年来,在 HIE 的动物模型中,也有几家实验室评估了干细胞/祖细胞移植的作用。研究表明,人脐带血单个核细胞和间充质干细胞/祖细胞可能通过在中枢神经系统局部和缺氧缺血动物的外周器官中发挥多种作用而具有治疗潜力。神经干细胞/祖细胞(NSCs)也已在 HIE 的动物模型中进行了移植,可长距离迁移到缺血性脑区并分化为神经元。这些研究结果提出了一些重要问题,在这些发现能够转化为临床应用之前,必须解决这些问题。在这篇综述中,我们对迄今为止发表的不同研究进行了批判性的概述,并讨论了新生儿大脑中 NSCs 在受到 HIE 损伤时的内源性再生潜力。我们还讨论了细胞疗法在早产儿脑病中的应用。