Wu Jiang, Sun Zhuo, Sun Hong-Shuo, Wu Jun, Weisel Richard D, Keating Armand, Li Zhi-Hong, Feng Zhong-Ping, Li Ren-Ke
Division of Cardiovascular Surgery, Toronto General Research Institute and University of Toronto, Toronto, Ontario, Canada.
Department of Neurology, Second Affiliated Hospital, Harbin Medical University, Harbin, China.
Cell Transplant. 2007 Nov;16(10):993-1005. doi: 10.3727/000000007783472435.
Accumulated evidence suggests that bone marrow stromal cells (BMSCs) are capable of regenerating damaged tissue. This study evaluated whether intravenously (noninvasively) administered, GFP-labeled BMSCs would migrate into damaged brain tissue and improve neurological function after a stroke. Wistar rats were subjected to middle cerebral artery occlusion and reperfusion. Twenty-four hours after injury, the rats received an IV injection of culture medium or BMSCs isolated from adult Wistar rats expressing green fluorescent protein (GFP). Two hours after injury and 1, 3, and 7 days after cell transplantation, neurological function was evaluated using a neurological severity scale. On day 7, the brain scar size was determined using tetrazolium chloride staining, and the implanted cells were identified using confocal microscopy. Immunohistochemistry was used to evaluate apoptosis and angiogenesis in the ischemic region, as well as the spatial distribution of the implanted BMSCs relative to the native neural cells. Implanted BMSCs migrated throughout the territory of the middle cerebral artery by 7 days after transplantation. Most implanted cells were located in the scar area and border zone of the ischemic region, and some expressed the neuronal marker NeuN. Rats receiving BMSC transplantation exhibited reduced scar size, limited apoptosis, and enhanced angiogenic factor expression and vascular density in the ischemic region relative to the control group, as well as significant improvements in the neurological severity scores. Intravenously administrated BMSCs facilitated the structural and functional recovery of neural tissue following ischemic injury, perhaps mediated by enhanced angiogenesis.
越来越多的证据表明，骨髓基质细胞（BMSCs）能够再生受损组织。本研究评估了静脉内（非侵入性）注射绿色荧光蛋白（GFP）标记的BMSCs是否会迁移至受损脑组织并改善中风后的神经功能。将Wistar大鼠进行大脑中动脉闭塞和再灌注。损伤后24小时，给大鼠静脉注射培养基或从表达绿色荧光蛋白（GFP）的成年Wistar大鼠分离的BMSCs。在损伤后2小时以及细胞移植后1、3和7天，使用神经严重程度量表评估神经功能。在第7天，使用氯化四氮唑染色确定脑瘢痕大小，并使用共聚焦显微镜鉴定植入的细胞。免疫组织化学用于评估缺血区域的细胞凋亡和血管生成，以及植入的BMSCs相对于天然神经细胞的空间分布。移植后7天，植入的BMSCs迁移至大脑中动脉的整个区域。大多数植入细胞位于缺血区域的瘢痕区域和边缘区，一些细胞表达神经元标志物NeuN。与对照组相比，接受BMSC移植的大鼠瘢痕大小减小、细胞凋亡受限、缺血区域血管生成因子表达增强和血管密度增加，并且神经严重程度评分有显著改善。静脉注射BMSCs促进了缺血性损伤后神经组织的结构和功能恢复，这可能是由增强的血管生成介导的。
