Synergistic effects of bone marrow stromal cells and a Rho kinase (ROCK) inhibitor, Fasudil on axon regeneration in rat spinal cord injury
Synergistic effects of bone marrow stromal cells and a Rho kinase (ROCK) inhibitor, Fasudil on axon regeneration in rat spinal cord injury
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DOI：
10.1111/j.1440-1789.2009.01077.x
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发表时间：
2010-06-01
期刊：
影响因子：
2.3
通讯作者：
Iwasaki, Yoshinobu
中科院分区：
文献类型：
--
作者：
Chiba, Yasuhiro;Kuroda, Satoshi;Iwasaki, Yoshinobu
移植的骨髓基质细胞通过多种机制促进脊髓损伤后的功能恢复。作为Rho激酶的抑制剂，法舒地尔也能促进轴突再生。本研究旨在评价骨髓间充质干细胞移植与法舒地尔联合治疗是否能进一步促进脊髓损伤大鼠的轴突再生和功能恢复。法舒地尔或赋形剂注射2周。伤后7d行骨髓间充质干细胞或载体移植至脊髓损伤吻端。在整个实验过程中，对神经症状进行了评估。伤后63天，将氟红宝石注射到脊髓损伤吻侧部位的背索内。免疫组织化学方法检测移植的骨髓间充质干细胞的命运。骨髓间充质干细胞移植可显著增加脊髓损伤尾侧皮质脊髓背侧纤维的数量，促进后肢功能恢复。部分移植的骨髓间充质干细胞的荧光红宝石、神经元特异性核蛋白和微管相关蛋白-2呈阳性，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联系。法舒地尔治疗也改善了轴突的连续性，但不能促进功能恢复。联合治疗可显著增加脊髓损伤尾侧皮质脊髓背侧纤维的数量，但不能进一步提高骨髓间充质干细胞移植对运动功能的治疗效果。这些结果表明，骨髓间充质干细胞移植和法舒地尔在脊髓损伤后轴突再生方面具有协同作用，尽管需要进一步的研究来进一步促进功能恢复。
Transplanted bone marrow stromal cells (BMSC) promote functional recovery after spinal cord injury (SCI) through multiple mechanisms. A Rho kinase inhibitor, Fasudil also enhances axonal regeneration. This study was aimed to evaluate whether combination therapy of BMSC transplantation and Fasudil further enhances axonal regeneration and functional recovery in rats subjected to SCI. Fasudil or vehicle was injected for 2 weeks. BMSC or vehicle transplantation into the rostral site of SCI was performed at 7 days after injury. Neurological symptoms were assessed throughout the experiments. Fluoro-Ruby was injected into the dorsal funiculus of the rostral site of SCI at 63 days after injury. The fate of the transplanted BMSC was examined using immunohistochemistry. BMSC transplantation significantly increased the number of Fluoro-Ruby -labeled fibers of the dorsal corticospinal tracts at the caudal site of SCI, enhancing functional recovery of the hind limbs. Some of the engrafted BMSC were positive for Fluoro-Ruby, neuronal specific nuclear protein and microtubule-associated protein-2, suggesting that they acquired neuronal phenotypes and built synaptic connection with the host's neural circuits. Fasudil treatment also improved axonal continuity, but did not promote functional recovery. Combination therapy dramatically increased the number of Fluoro-Ruby-labeled fibers of the dorsal corticospinal tracts at the caudal site of SCI, but did not further boost the therapeutic effects on locomotor function by BMSC transplantation. The findings suggest that BMSC transplantation and Fasudil provide synergistic effects on axon regeneration after SCI, although further studies would be necessary to further enhance functional recovery.