Multiple injections of human umbilical cord-derived mesenchymal stromal cells through the tail vein improve microcirculation and the microenvironment in a rat model of radiation myelopathy
Multiple injections of human umbilical cord-derived mesenchymal stromal cells through the tail vein improve microcirculation and the microenvironment in a rat model of radiation myelopathy
复制标题
通过尾静脉多次注射人脐带间充质基质细胞改善放射性脊髓病大鼠模型的微循环和微环境
DOI：
10.1186/s12967-014-0246-6
复制
发表时间：
2014-09-08
影响因子：
7.4
通讯作者：
You, Hua
中科院分区：
文献类型：
--
作者：
Wei, Li;Zhang, Jing;You, Hua
背景放射性脊髓病的迟发效应目前尚无有效的治疗方法。本研究的目的是评估人脐带间充质干细胞（UC-MSCs）在放射性脊髓病大鼠模型中的治疗效果。在照射后90、97、104和111天通过尾静脉注射UC-MSC。采用前肢麻痹评分系统进行行为学测试，并采用尼氏染色检查组织学损伤。采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微循环。通过测定血清中促炎细胞因子白细胞介素-1 β（IL-1β）和肿瘤坏死因子-α（TNF-α）以及脊髓中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。减少脊髓组织学损伤，增加脊髓前角中的神经元数量，增加脊髓白色物质和灰质中的内皮细胞密度和微血管密度，增加脊髓血流量的相对大小，下调血清中促炎细胞因子的表达，并增加抗炎细胞因子在脊髓中的表达。ConclusionMultiple injection of UC-MSCs via the tail vein in in a rat model of radiation myelopathy significantly improved the microcirculation and microenvironment through therapeutic paracrine effects.
BackgroundAt 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.MethodsAn 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.ResultsMultiple 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.ConclusionMultiple 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.