Intraarterial administration of marrow stromal cells in a rat model of traumatic brain injury
Intraarterial administration of marrow stromal cells in a rat model of traumatic brain injury
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DOI：
10.1089/089771501316919175
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发表时间：
2001-08-01
影响因子：
4.2
通讯作者：
Chopp, M
中科院分区：
文献类型：
--
作者：
Lu, DY;Li, Y;Chopp, M
为了测试干细胞不同输送途径治疗脑损伤的功效，我们研究了创伤性脑损伤（TBI）后注射到成年大鼠颈内动脉（ICA）中的骨髓基质细胞（MSC）的实质分布。 TBI 后 24 小时通过同侧 ICA 注射溴脱氧尿苷 (BrdU) 标记的 MSC。使用组织学和免疫组织化学，在移植后 7 天分析植入的 MSC 的分布。研究分为四组（n = 4/组）：第 1 组，TBI 后 24 小时移植用 NGF 和 BDNF 培养的 MSC 的动物；第2组，移植无NGF和BDNF培养的MSC的动物；第3组，TBI后24小时将安慰剂、磷酸盐缓冲盐水注射到ICA中；第4组，仅接受TBI的大鼠。在第1组和第2组中，BrdU阳性细胞定位于病变边界区、胼胝体和同侧半球皮质。同侧半球的 BrdU 阳性细胞数量显着高于对侧半球。第 1 组 (18.9%) 中动脉内输注的 MSC 多于第 2 组 (14.4%，p < 0.05)。使用双染色法，BrdU 阳性细胞在第 1 组和第 2 组中均表达 MAP-2、NeuN 和 GFAP，其中第 1 组的表达量更高，并且在 MAP-2 的情况下，两组之间的差异达到统计学显着性。我们的数据表明，动脉内移植 MSC 是脑内注射 MSC 治疗 TBI 的可行途径，因为 TBI 后动脉内注入的 MSC 能够存活并迁移到大脑中。一些植入的间充质干细胞表达神经元和星形胶质细胞特有的蛋白质。添加 NGF 和 BDNF 可促进 MSC 迁移至大脑并随后表达神经元蛋白 MAP-2。
To test the efficacy of various delivery routes of stem cells to treat cerebral injury, we investigated the parenchymal distribution of marrow stromal cells (MSCs) injected into the internal carotid artery (ICA) of the adult rat after traumatic brain injury (TBI). Bromodeoxyuridine (BrdU)-labeled MSCs were injected via the ipsilateral ICA at 24 h after TBI. Using histology and immunohistochemistry, the distribution of implanted MSCs was analyzed at 7 days after transplantation. Four groups (n = 4/group) were studied: group 1, animals transplanted with MSCs cultured with NGF and BDNF at 24 h after TBI; group 2, animals transplanted with MSCs cultured without NGF and BDNF; group 3, animals injected with a placebo, phosphate buffered saline into the ICA at 24 h after TBI; and group 4, rats subjected to TBI only. In groups 1 and 2, BrdU-positive cells were localized to the boundary zone of the lesion, corpus callosum and cortex of the ipsilateral hemisphere. The number of BrdU-positive cells was significantly higher in the ipsilateral hemisphere than in the contralateral hemisphere. More MSCs infused intraarterially engrafted in group 1 (18.9%) than in group 2 (14.4%, p < 0.05). Using double staining, BrdU-positive cells expressed MAP-2, NeuN, and GFAP in both groups 1 and 2, with this expression being greater in group 1 and the difference between two groups reaching statistical significance in case of MAP-2. Our data suggest that intraarterial transplantation of MSCs is a viable route for the intracerebral administration of MSCs for the treatment of TBI, since MSCs infused intraarterially after TBI survive and migrate into the brain. Some implanted MSCs express proteins specific to neurons and astrocytes. The addition of NGF and BDNF promote migration of MSCs into the brain and subsequent expression of neuronal protein MAP-2.