Li Yi, McIntosh Kevin, Chen Jieli, Zhang Chunling, Gao Qi, Borneman Jade, Raginski Kim, Mitchell James, Shen Lihong, Zhang Jing, Lu Dunyue, Chopp Michael
Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Exp Neurol. 2006 Apr;198(2):313-25. doi: 10.1016/j.expneurol.2005.11.029. Epub 2006 Feb 7.
We evaluated the effects of allogeneic bone marrow stromal cell treatment of stroke on functional outcome, glial-axonal architecture, and immune reaction. Female Wistar rats were subjected to 2 h of middle cerebral artery occlusion. Rats were injected intravenously with PBS, male allogeneic ACI--or syngeneic Wistar--bone marrow stromal cells at 24 h after ischemia and sacrificed at 28 days. Significant functional recovery was found in both cell-treated groups compared to stroke rats that did not receive BMSCs, but no difference was detected between allogeneic and syngeneic cell-treated rats. No evidence of T cell priming or humoral antibody production to marrow stromal cells was found in recipient rats after treatment with allogeneic cells. Similar numbers of Y-chromosome+ cells were detected in the female rat brains in both groups. Significantly increased thickness of individual axons and myelin, and areas of the corpus callosum and the numbers of white matter bundles in the striatum were detected in the ischemic boundary zone of cell-treated rats compared to stroked rats. The areas of the contralateral corpus callosum significantly increased after cell treatment compared to normal rats. Processes of astrocytes remodeled from hypertrophic star-like to tadpole-like shape and oriented parallel to the ischemic regions after cell treatment. Axonal projections emanating from individual parenchymal neurons exhibited an overall orientation parallel to elongated radial processes of reactive astrocytes of the cell-treated rats. Allogeneic and syngeneic bone marrow stromal cell treatment after stroke in rats improved neurological recovery and enhanced reactive oligodendrocyte and astrocyte related axonal remodeling with no indication of immunologic sensitization in adult rat brain.
我们评估了同种异体骨髓基质细胞治疗中风对功能结局、神经胶质-轴突结构和免疫反应的影响。雌性Wistar大鼠接受2小时的大脑中动脉闭塞。大鼠在缺血后24小时静脉注射磷酸盐缓冲盐水(PBS)、雄性同种异体ACI或同基因Wistar骨髓基质细胞,并在28天时处死。与未接受骨髓间充质干细胞(BMSCs)的中风大鼠相比,两个细胞治疗组均发现有显著的功能恢复,但同种异体和同基因细胞治疗的大鼠之间未检测到差异。在用同种异体细胞治疗后,受体大鼠中未发现对骨髓基质细胞的T细胞致敏或体液抗体产生的证据。两组雌性大鼠大脑中检测到的Y染色体阳性细胞数量相似。与中风大鼠相比,在细胞治疗大鼠的缺血边界区检测到单个轴突和髓鞘厚度显著增加,胼胝体面积和纹状体白质束数量增加。与正常大鼠相比,细胞治疗后对侧胼胝体面积显著增加。细胞治疗后,星形胶质细胞的形态从肥大的星形重塑为蝌蚪状,并与缺血区域平行排列。来自单个实质神经元的轴突投射总体上与细胞治疗大鼠反应性星形胶质细胞的细长放射状突起平行。大鼠中风后同种异体和同基因骨髓基质细胞治疗可改善神经功能恢复,并增强反应性少突胶质细胞和星形胶质细胞相关的轴突重塑,且在成年大鼠脑中未显示免疫致敏迹象。