Intra-arterial delivery is not superior to intravenous delivery of autologous bone marrow mononuclear cells in acute ischemic stroke.
Intra-arterial delivery is not superior to intravenous delivery of autologous bone marrow mononuclear cells in acute ischemic stroke.
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DOI：
10.1161/strokeaha.111.000821
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发表时间：
2013-12
期刊：
影响因子：
8.3
通讯作者：
Savitz SI
中科院分区：
文献类型：
--
作者：
Yang B;Migliati E;Parsha K;Schaar K;Xi X;Aronowski J;Savitz SI
骨髓源性单核细胞（mnc）是一种基于自体细胞的急性缺血性脑卒中治疗方法。静脉（IV）和动脉（IA）给药途径已在临床试验中使用。然而，优化跨国公司效果的管理途径尚不清楚。在本研究中，我们比较了IV和IA途径对大鼠脑卒中模型的影响。对Long Evans大鼠进行短暂性大脑中动脉闭塞（MCAo）治疗。在中风后24小时，动物被随机分配通过静脉注射或内注射途径接受自体骨髓来源的MNCs。静脉生理盐水作为对照。评估100万个细胞/kg（低剂量）和3000万个细胞/kg（高剂量）。评估神经学测试、空腔大小、血清细胞因子、神经再生终点和MNC生物分布。与生理盐水治疗相比，高剂量MNCs可改善功能恢复，减少病变大小和促炎细胞因子，增加血管密度和神经发生标志物（p<0.05）。然而，IV和IA MNC治疗组之间无显著差异；然而，IV MNCs与IA MNCs相比，血清IL-1β水平降低（p<0.05）。高剂量的IA MNCs在注射后1和6小时导致脑内细胞数量增加，但在肺和脾脏中没有。与生理盐水相比，低剂量MNCs （IV或IA）没有改善任何功能或结构终点。在低剂量和高剂量的MNCs中，我们发现IV或IA在卒中后达到相似的结构和功能结果。
Bone marrow derived mononuclear cells (MNCs) are an investigational autologous cell-based therapy for acute ischemic stroke. Both intravenous (IV) and intra-arterial (IA) administration routes have been used in clinical trials. However, the route of administration to optimize the effect of MNCs is unknown. In this study, we compared the effect of IV versus IA route of MNCs in the rat stroke model. Long Evans rats were subjected to transient middle cerebral artery occlusion (MCAo). At 24 hrs after stroke, animals were randomly assigned to either receive autologous bone marrow derived MNCs using IV or IA delivery routes. IV saline served as control. 1 million cells/kg (low dose) and 30 million cells/kg (high dose) were assessed. Neurological testing, cavity size, serum cytokines, neuroregenerative endpoints, and MNC biodistribution were evaluated. High dose MNCs improved functional recovery, reduced lesion size and pro-inflammatory cytokines, and increased vessel density and neurogenesis markers compared with saline treatment (p<0.05). However, there were no significant differences between IV and IA MNC treated groups; though, IV MNCs reduced serum IL-1β levels compared with IA MNCs (p<0.05). IA MNCs at high dose led to a greater number of cells in the brain at 1 and 6 hrs after injection but not in the lungs and spleen. Low dose MNCs (by IV or IA) did not improve any functional or structural endpoint compared with saline. At low and high doses of MNCs, we found that IV or IA achieves similar structural and functional outcomes after stroke.