University of California San Diego, School of Medicine, Departments of Pediatrics, USA.
Exp Neurol. 2010 Oct;225(2):284-93. doi: 10.1016/j.expneurol.2010.06.001. Epub 2010 Jun 12.
Stroke is a major cause of mortality and morbidity in the United States. The ideal therapeutic approach would minimize cell death and regenerate brain tissue. In order to investigate some questions that are related to such an approach, we have generated a mouse model in which we induce a stroke using the middle cerebral artery occlusion method. After 2h occlusion followed by reperfusion, 99% of mice died within 8 days of stroke. Total bone marrow cell transplantation by intravenous injection revealed an optimal timing of cell transfer in two doses on days 1 (same day of surgery) and 2 after surgery. Moreover, intravenous injection of Sca1+ bone marrow cells (enriched in hematopoietic stem cells) showed a dose-response effect on survival. Surviving mice also had no signs of apparent paralysis or weakness. Tracking analysis using donor stem cells expressing LacZ revealed only few donor cells in the brain. We conclude that hematopoietic stem cell-rich Sca1+ bone marrow cell transplantation after stroke protects the brain of a sizeable portion of mice subjected to stroke and alleviate remarkably the resulting neurological morbidity in surviving mice.
中风是美国主要的致死和致残原因。理想的治疗方法是最大限度地减少细胞死亡并再生脑组织。为了研究与这种方法相关的一些问题，我们使用大脑中动脉闭塞法生成了一种中风小鼠模型。在闭塞 2 小时后再灌注，99%的中风后小鼠在 8 天内死亡。通过静脉注射进行全骨髓细胞移植显示，在手术后第 1 天（同一天）和第 2 天进行两次细胞转移的最佳时机。此外，静脉注射 Sca1+骨髓细胞（富含造血干细胞）对存活率具有剂量反应效应。存活的小鼠也没有明显瘫痪或虚弱的迹象。使用表达 LacZ 的供体干细胞进行跟踪分析表明，大脑中只有少数供体细胞。我们的结论是，中风后富含造血干细胞的 Sca1+骨髓细胞移植可保护相当一部分中风小鼠的大脑，并显著减轻存活小鼠的神经发病率。
