Therapeutic window for treatment of cortical ischemia with bone marrow-derived cells in rats
Therapeutic window for treatment of cortical ischemia with bone marrow-derived cells in rats
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DOI：
10.1016/j.brainres.2009.09.094
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发表时间：
2010-01-08
期刊：
影响因子：
2.9
通讯作者：
Mendez-Otero, Rosalia
中科院分区：
文献类型：
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作者：
dos Santos, Andreia de Vasconcelos;Reis, Juliana da Costa;Mendez-Otero, Rosalia
在热凝左运动区、中脑区和感觉运动区的血管所致的局灶性脑缺血大鼠模型上，观察了不同治疗窗对骨髓单个核细胞(BMMCs)治疗的有益效果。我们还比较了骨髓间充质干细胞和骨髓间充质干细胞之间的治疗效果。取供体大鼠的骨髓间充质干细胞和骨髓间充质干细胞，缺血后注入颈静脉。BMMCs处理的动物在缺血后1天、7天、14天或30天接受大约3x10(7)个细胞。MSCs处理的动物在PID为1和30时获得了大约3x10(6)个细胞。对照组动物只接受了交通工具。然后每周用行为学测试(气缸测试和粘连测试)评估动物的感觉运动功能恢复情况。感觉运动功能仅在第1天和第7天BMMCs组有显著恢复。MSCs组在缺血1d后也有类似的效果，而MSCs组在缺血后30d没有观察到类似的效果。胶质瘢痕的显著减少似乎不是BMMCs的作用机制，因为BMMCs治疗没有改变GFAP的表达水平，表明缺血灶周围的星形细胞瘢痕没有显著变化。这些结果提示，BMMCs可能仅在急性/亚急性期才是一种有效的治疗方案，其诱导功能恢复的效果与MSCs相似。(C)2009爱思唯尔B.V.保留所有权利。
The beneficial effect of treatment with bone marrow mononuclear cells (BMMCs) was evaluated in different therapeutic windows in a rat model of focal ischemia induced by thermocoagulation of the blood vessels in the left motor, somestesic, and sensorimotor cortices. We also compared the therapeutic benefits between BMMCs and bone marrow-derived mesenchymal stem cells (MSCs). BMMCs and MSCs were obtained from donor rats and injected into the jugular vein after ischemia. BMMCs-treated animals received approximately 3 x 10(7) cells at post-ischemic days (PIDs) 1, 7, 14, or 30. MSCs-treated animals received approximately 3 x 10(6) cells at PIDs 1 and 30. Control animals received only the vehicle. The animals were then evaluated for functional sensorimotor recovery weekly with behavioral tests (cylinder test and adhesive test). Significant recovery of sensorimotor function was only observed in the cylinder test in animals treated with BMMCs at PIDs 1 and 7. Similar effects were also observed in the animals treated with MSCs 1 day after ischemia, but not in animals treated with MSCs 30 days after ischemia. Significant decrease in glial scarring did not seem to be a mechanism of action of BMMCs, since treatment with BMMCs did not change the level of expression of GFAP, indicating no significant change in the astrocytic scar in the periphery of the ischemic lesion. These results suggest that BMMCs might be an efficient treatment protocol for stroke only in the acute/subacute phase of the disease, and its efficiency in inducing functional recovery is similar to that of MSCs. (C) 2009 Elsevier B.V. All rights reserved.