Wei Li, Zhang Jing, Xiao Xiu-Bin, Mai Hai-Xing, Zheng Ke, Sun Wan-Liang, Wang Lei, Liang Feng, Yang Zai-Liang, Liu Yuan, Wang Yan-Qing, Li Zhi-Fang, Wang Jia-Ning, Zhang Wei-Jing, You Hua
J Transl Med. 2014 Sep 8;12:246. doi: 10.1186/s12967-014-0246-6.
At present, no effective clinical treatment is available for the late effects of radiation myelopathy. The aim of the present study was to assess the therapeutic effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy.
An irradiated cervical spinal cord rat model was generated. UC-MSCs were injected through the tail vein at 90, 97, 104 and 111 days post-irradiation. Behavioral tests were performed using the forelimb paralysis scoring system, and histological damage was examined using Nissl staining. The microcirculation in the spinal cord was assessed using von Willebrand factor (vWF) immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the spinal cord.
Multiple injections of UC-MSCs through the tail veil decreased the forelimb paralysis, decreased spinal cord histological damage, increased the number of neurons in the anterior horn of the spinal cord, increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, increased the relative magnitude of spinal cord blood flow, down-regulated pro-inflammatory cytokine expression in the serum, and increased anti-inflammatory cytokine expression in the spinal cord.
Multiple injections of UC-MSCs via the tail vein in a rat model of radiation myelopathy significantly improved the microcirculation and microenvironment through therapeutic paracrine effects.
目前，对于放射性脊髓病的晚期效应尚无有效的临床治疗方法。本研究的目的是评估人脐带间充质基质细胞（UC-MSCs）在放射性脊髓病大鼠模型中的治疗效果。
建立照射后颈段脊髓大鼠模型。在照射后90、97、104和111天通过尾静脉注射UC-MSCs。使用前肢麻痹评分系统进行行为测试，并用尼氏染色检查组织学损伤。使用血管性血友病因子（vWF）免疫组织化学分析和激光多普勒血流仪评估脊髓中的微循环。通过测量血清中的促炎细胞因子白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）以及脊髓中的抗炎细胞因子脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）来确定脊髓中的微环境。
通过尾静脉多次注射UC-MSCs可减轻前肢麻痹，减轻脊髓组织学损伤，增加脊髓前角神经元数量，增加脊髓白质和灰质中的内皮细胞密度和微血管密度，增加脊髓血流的相对幅度，下调血清中促炎细胞因子的表达，并增加脊髓中抗炎细胞因子的表达。
在放射性脊髓病大鼠模型中通过尾静脉多次注射UC-MSCs可通过治疗旁分泌作用显著改善微循环和微环境。
