Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement.
Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement.
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DOI：
10.1371/journal.pone.0051253
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Heijnen CJ
中科院分区：
文献类型：
--
作者：
Donega V;van Velthoven CT;Nijboer CH;van Bel F;Kas MJ;Kavelaars A;Heijnen CJ
间充质干细胞（MSC）经鼻给药可能成为治疗新生儿缺氧缺血性脑损伤的有效方法。我们分析了鼻内MSC治疗对病变大小、感觉运动和认知行为的长期影响，并确定了治疗窗口和剂量反应关系。此外，我们还检查了MSCs在病变部位的外观与治疗窗口的关系。9日龄小鼠单侧颈动脉闭塞和缺氧。在缺氧缺血（HI）后3、10或17天经鼻给药MSCs。观察运动、认知和组织学结果。用PKH-26标记的细胞定位脑内间充质干细胞。我们确定0.5×106间充质干细胞为最小有效剂量，治疗窗口期在hi后至少为10天但少于17天。单次剂量就足以产生显著的有益效果。损伤后3天或10天给予间充质干细胞，可在24小时内到达病变部位。然而，在HI后17天给药时，病变中未检测到MSCs。我们也首次表明HI后鼻内骨髓间充质干细胞治疗可改善认知功能。感觉运动功能和组织学结果的改善至少维持到hi后9周。经鼻给药后10天，MSCs在24小时内到达病变部位的能力，而在hi后17天则没有，这表明至少有10天的治疗窗口期。我们的数据强烈表明，鼻内骨髓间充质干细胞治疗可能成为有效减少新生儿脑病的一种有前途的非侵入性治疗工具。
Mesenchymal stem cell (MSC) administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI) brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI). Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5×106 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy.
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影响因子：
5.3
作者：
Nijboer, Cora H. A.;Kavelaars, Annemieke;Heijnen, Cobi J.
通讯作者：
Heijnen, Cobi J.
影响因子：
5.3
作者：
van Velthoven, Cindy T. J.;Kavelaars, Annemieke;Heijnen, Cobi J.
通讯作者：
Heijnen, Cobi J.
静脉移植物概括了新生儿低氧 - 缺血性大鼠中脑部递送的多能祖细胞提供的神经修养。
影响因子：
6.3
作者：
Yasuhara, Takao;Hara, Koichi;Maki, Mina;Mays, Robert W.;Deans, Robert J.;Hess, David C.;Carroll, James E.;Borlongan, Cesar V.
通讯作者：
Borlongan, Cesar V.
影响因子：
3.6
作者：
Borlongan CV;Weiss MD
通讯作者：
Weiss MD
影响因子：
3.6
作者：
Lee, Jin A.;Kim, Beyong Il;Choi, Jung-Hwan
通讯作者：
Choi, Jung-Hwan