Transplantation of human bone marrow stromal cell-derived Schwann cells reduces cystic cavity and promotes functional recovery after contusion injury of adult rat spinal cord

Transplantation of human bone marrow stromal cell-derived Schwann cells reduces cystic cavity and promotes functional recovery after contusion injury of adult rat spinal cord
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DOI:
10.1111/j.1440-1789.2010.01130.x
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发表时间:
2011-02-01
期刊:
影响因子:
2.3
通讯作者:
Yamazaki, Masashi
Yamazaki, Masashi
中科院分区:
医学4区
文献类型:
--
作者:
Kamada, Takahito;Koda, Masao;Yamazaki, Masashi

文献摘要

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本研究旨在评价人骨髓基质细胞来源的雪旺细胞(hBMSC-SC)移植对成年大鼠脊髓挫伤后功能恢复的影响。从成人骨髓中分离培养出人骨髓基质细胞(HBMSC),体外诱导为雪旺细胞(hBMSC-SC)。免疫细胞化学检测雪旺细胞表型。用细胞因子抗体阵列检测hBMSC-SC分泌的生长因子。免疫抑制大鼠切除椎板,用NYU冲击器(10g,25 mm)挫伤脊髓。伤后第9天,将Matrigel和hBMSC-SC的混合物(hBMSC-SC组)注入损伤部位。移植后5周,甲酚紫染色显示hBMSC-SC组囊腔面积小于对照组。免疫组织化学结果显示,hBMSC-SC组的抗生长相关蛋白-43阳性神经纤维数量明显多于对照组。同时,hBMSC-SC组损伤中心和尾侧水平的酪氨酸羟基酶或5-羟色胺阳性纤维数量明显多于对照组。在电子显微镜下,hBMSC-SC组在病变中心附近可见周围型髓鞘形成。与对照组相比,hBMSC-SC组大鼠后肢功能明显恢复。综上所述,hBMSC-SC在大鼠脊髓损伤模型中的功能与原始雪旺细胞相当,因此hBMSC-SC对脊髓损伤患者具有潜在的治疗作用。
The aim of this study was to evaluate whether transplantation of human bone marrow stromal cell-derived Schwann cells (hBMSC-SC) promotes functional recovery after contusive spinal cord injury of adult rats. Human bone marrow stromal cells (hBMSC) were cultured from bone marrow of adult human patients and induced into Schwann cells (hBMSC-SC) in vitro. Schwann cell phenotype was confirmed by immunocytochemistry. Growth factors secreted from hBMSC-SC were detected using cytokine antibody array. Immunosppressed rats were laminectomized and their spinal cords were contused using NYU impactor (10 g, 25 mm). Nine days after injury, a mixture of Matrigel and hBMSC-SC (hBMSC-SC group) was injected into the lesioned site. Five weeks after transplantation, cresyl-violet staining revealed that the area of cystic cavity was smaller in the hBMSC-SC group than that in the control group. Immunohistochemstry revealed that the number of anti-growth-associated protein-43-positive nerve fibers was significantly larger in the hBMSC-SC group than that in the control group. At the same time, the number of tyrosine hydroxylase- or serotonin-positive fibers was significantly larger at the lesion epicenter and caudal level in the hBMSC-SC group than that in the control group. In electron microscopy, formation of peripheral-type myelin was recognized near the lesion epicenter in the hBMSC-SC group. Hind limb function recovered significantly in the hBMSC-SC group compared with the control group. In conclusion, the functions of hBMSC-SC are comparable to original Schwann cells in rat spinal cord injury models, and are thus potentially useful treatments for patients with spinal cord injury.