Mesenchymal Stem-Cell Transplantation for Hypoxic-Ischemic Brain Injury in Neonatal Rat Model
Mesenchymal Stem-Cell Transplantation for Hypoxic-Ischemic Brain Injury in Neonatal Rat Model
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DOI：
10.1203/pdr.0b013e3181bf594b
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发表时间：
2010-01-01
影响因子：
3.6
通讯作者：
Choi, Jung-Hwan
中科院分区：
文献类型：
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作者：
Lee, Jin A.;Kim, Beyong Il;Choi, Jung-Hwan
新生儿缺氧缺血性脑损伤（hypoxic-ischemic brain injury，HIE）是导致神经功能障碍的主要原因。然而，许多实验性疗法显示出有限的成功。我们评估了是否可以将人间充质干细胞（MSC）移植到HIE大鼠脑中以改善神经功能障碍。P7 SD大鼠行左颈总动脉结扎和低氧暴露（hypoxia-ischemia，HI）或假手术和常氧暴露（sham）。在P10，大鼠pub通过心内注射接受PKH 26标记的MSC或缓冲液，产生四个实验组：假缓冲液，假MSC，HI缓冲液。和HI-MSC。注射后14、20、307和40 d进行圆筒试验和加速转棒试验。注射后6周，进行甲酚紫和双重免疫荧光染色。骨髓间充质干细胞主要在HI后移植至全脑。胶质细胞酸性蛋白和OX 42与MSC的共定位比神经元特异性核蛋白和髓鞘碱性蛋白更丰富。损伤侧和非损伤侧的细胞总数和细胞类型无显著差异。损伤半球体积减少后HI（p = 0.012），但没有恢复MSC。神经功能仅在HI后的圆筒试验中显著受损（p = 0.034），MSC移植改善了神经功能（p = 0.010）。这些结果提示MSC可作为治疗新生儿HIE的候选药物。（Pediatr Res 67：42-46，2010）
Neonatal hypoxic-ischemic brain injury (HIE) remains a major cause of neurologic disabilities. However, many experimental therapies have shown limited successes. We assessed whether human mesenchymal stem cells (MSCs) could be transplanted in the HIE rat brain to improve neurologic disabilities. P7 SD rats were either subjected to left carotid artery ligation and hypoxic exposure [hypoxia-ischemia (HI)) or sham operation and normoxic exposure (sham). On P10, rat pubs received either PKH26-labeled MSCs or buffer via intracardial injection, resulting in four experimental groups: sham-buffer, sham-MSC, HI-buffer. and HI-MSC. Cylinder test and accelerating rotarod test were performed 14, 20 307 and 40 d after injection. Six weeks after injection, cresyl violet and double immunofluorescence staining were performed. MSCs were transplanted to the whole brain mainly after HI. Glial fibrillary acidic protein and OX42 were more abundantly colocalized with MSC than neuronal specific nuclear protein or myelin basic protein. There were no significant differences in the total amounts and cell types between the lesioned and nonlesioned hemisphere. The lesioned hemispheric volume was decreased after HI (p = 0.012) but not restored by MSC. Neurologic performance was significantly impaired only on the cylinder test after HI (p = 0.034), and MSC transplants improved it (p = 0.010). These suggest MSC can be a candidate for the treatment of neonatal HIE. (Pediatr Res 67: 42-46, 2010)