TRANSPLANTED BONE MARROW STROMAL CELLS PROMOTE AXONAL REGENERATION AND IMPROVE MOTOR FUNCTION IN A RAT SPINAL CORD INJURY MODEL

TRANSPLANTED BONE MARROW STROMAL CELLS PROMOTE AXONAL REGENERATION AND IMPROVE MOTOR FUNCTION IN A RAT SPINAL CORD INJURY MODEL
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DOI:
10.1227/01.neu.0000341905.57162.1d
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发表时间:
2009-05-01
期刊:
影响因子:
4.8
通讯作者:
Iwasaki, Yoshinobu
Iwasaki, Yoshinobu
中科院分区:
医学1区
文献类型:
--
作者:
Chiba, Yasuhiro;Kuroda, Satoshi;Iwasaki, Yoshinobu

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目的:最近的研究表明,骨髓基质细胞(BMSC)移植到脊髓损伤(SCI)动物模型中具有改善神经功能的潜力。然而,目前尚不清楚移植的BMSCs如何促进SCI后的功能恢复。因此,在本研究中,我们评估了移植的骨髓间充质干细胞如何恢复受损脊髓中背侧皮质脊髓束的功能。方法:通过气动冲击G装置对大鼠进行不完全SCI。损伤后 7 天将 BMSC 或载体移植到 SCI 的喙部部位。在整个实验过程中评估神经系统症状。损伤后 63 天,将 I Fluoro-Ruby 注射到 SCI 头侧部位的背索中。使用免疫组织化学检查移植的BMSC的命运。结果:BMSC移植显着促进后肢的功能恢复。 BMSC 移植动物中 SCI 尾部背侧皮质脊髓束的氟红宝石标记纤维数量显着高于载体移植动物。一些移植的 BMSC 在灰质中呈 Fluoro-Ruby、NeuN 和 MAP2 阳性,表明它们获得了神经元表型并与宿主的神经回路建立了突触连接。白质中的其他细胞在形态上模拟星形胶质细胞,胶质纤维酸性蛋白 I 也呈阳性。 结论:研究结果表明,移植的 BMSC 获得了损伤部位周围的神经细胞表型,有助于重建包括皮质脊髓束在内的神经回路,促进后肢功能恢复。
OBJECTIVE: Recent studies have indicated that bone marrow stromal cells (BMSCs) have the potential to improve neurological function when transplanted into animal models of spinal cord injury (SCI). However, it is still unclear how the transplanted BMSCs promote functional recovery after SCI. In this study, therefore, we evaluated how the transplanted BMSCs restore the function of the dorsal corticospinal tracts in the injured spinal cord.METHODS: The rats were subjected to incomplete SCI by means of a pneumatic impact G device. BMSC or vehicle transplantation into the rostral site of SCI was performed at 7 days after injury. Neurological symptoms were assessed throughout the experiments. I Fluoro-Ruby was injected into the dorsal funiculus of the rostral site of SCI at 63 days after injury. The fate of the transplanted BMSCs was examined using immunohistochemistry.RESULTS: BMSC transplantation significantly enhanced functional recovery of the hind limbs. The number of Fluoro-Ruby-labeled fibers of the dorsal corticospinal tracts at the caudal site of SCI was significantly higher in the BMSC-transplanted animals than in the vehicle-transplanted animals. Some of the engrafted BMSCs were positive for Fluoro-Ruby, NeuN, and MAP2 in the gray matter, suggesting that they acquired neuronal phenotypes and built synaptic connection with the host's neural circuits. Others in the white matter morphologically simulated the astrocytes and were also positive I for glial fibrillary acidic protein.CONCLUSION: The findings suggest that the transplanted BMSCs acquire neural cell phenotypes around the injury site and contribute to rebuild the neural circuits, including the corticospinal tract, promoting functional recovery of the hind limbs.