Chiba Yasuhiro, Kuroda Satoshi, Maruichi Katsuhiko, Osanai Toshiya, Hokari Masaaki, Yano Shunsuke, Shichinohe Hideo, Hida Kazutoshi, Iwasaki Yoshinobu
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Neurosurgery. 2009 May;64(5):991-9; discussion 999-1000. doi: 10.1227/01.NEU.0000341905.57162.1D.
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.
The rats were subjected to incomplete SCI by means of a pneumatic impact 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. 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.
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 for glial fibrillary acidic protein.
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.
近期研究表明，骨髓基质细胞（BMSCs）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BMSCs如何恢复受损脊髓中皮质脊髓束的功能。
通过气动冲击装置对大鼠造成不完全性SCI。在损伤后7天，将BMSCs或载体移植到SCI的头端部位。在整个实验过程中评估神经症状。在损伤后63天，将荧光红宝石注入SCI头端部位的背侧索。使用免疫组织化学检查移植的BMSCs的命运。
BMSCs移植显著增强了后肢的功能恢复。在SCI尾端部位，BMSCs移植组动物的皮质脊髓束中荧光红宝石标记的纤维数量明显高于载体移植组动物。一些植入的BMSCs在灰质中对荧光红宝石、NeuN和MAP2呈阳性，表明它们获得了神经元表型并与宿主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，并且对胶质纤维酸性蛋白也呈阳性。
研究结果表明，移植的BMSCs在损伤部位周围获得神经细胞表型，并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。
