Long-Lasting Paracrine Effects of Human Cord Blood Cells on Damaged Neocortex in an Animal Model of Cerebral Palsy
Long-Lasting Paracrine Effects of Human Cord Blood Cells on Damaged Neocortex in an Animal Model of Cerebral Palsy
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DOI：
10.3727/096368912x640457
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发表时间：
2012-01-01
影响因子：
3.3
通讯作者：
Moon, Jisook
中科院分区：
文献类型：
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作者：
Bae, Sang-Hun;Kong, Tae-Ho;Moon, Jisook
新生儿窒息是脑性瘫痪（CP）的一个重要因素，目前尚无有效的治疗方法。人脐带血细胞（hUCBCs）的给药正在成为治疗神经系统疾病的治疗策略。然而，很少有关于hUCBCs作为CP模型用于治疗新生儿缺血的研究。对新生儿缺氧/缺血进行的实验和行为测试（主要是运动测试）仅限于hUCBCs的短期效应，但尚未研究其作用机制。我们在新生儿缺氧/缺血的大鼠模型中使用hUCBC进行了研究，并研究了hUCBC治疗的治疗益处的潜在机制。将hUCBCs静脉移植到新生大鼠缺氧缺血模型中。hUCBCs在疾病的早期阶段暂时增加了室周纹状体中的小胶质细胞，保护了新皮层中的成熟神经元免受损伤，为室下区（SVZ）中脑损伤的接近正常化铺平了道路，并且因此，与媒介物治疗组相比，显著改善了一系列行为测试中的表现。虽然移植后3周在大脑中很少观察到移植细胞，但改善行为功能的效果持续存在。我们的临床前研究结果表明，hUCBCs的持久积极影响源自hUCBCs的旁分泌效应，可刺激受伤大脑的恢复并防止进一步的脑损伤。
Neonatal asphyxia is an important contributor to cerebral palsy (CP), for which there is no effective treatment to date. The administration of human cord blood cells (hUCBCs) is emerging as a therapeutic strategy for the treatment of neurological disorders. However, there are few studies on the application of hUCBCs to the treatment of neonatal ischemia as a model of CP. Experiments and behavioral tests (mainly motor tests) performed on neonatal hypoxia/ischemia have been limited to short-term effects of hUCBCs, but mechanisms of action have not been investigated. We performed a study on the use of hUCBCs in a rat model of neonatal hypoxia/ischemia and investigated the underlying mechanism for therapeutic benefits of hUCBC treatment. hUCBCs were intravenously transplanted into a rat model of neonatal hypoxia ischemia. hUCBCs increased microglia temporarily in the periventricular striatum in the early phase of disease, protected mature neurons in the neocortex from injury, paved the way for the near-normalization of brain damage in the subventricular zone (SVZ), and, in consequence, significantly improved performance in a battery of behavioral tests compared to the vehicle-treated group. Although the transplanted cells were rarely observed in the brain 3 weeks after transplantation, the effects of the improved behavioral functions persisted. Our preclinical findings suggest that the long-lasting positive influence of hUCBCs is derived from paracrine effects of hUCBCs that stimulate recovery in the injured brain and protect against further brain damage.