Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA, USA.
PLoS One. 2013;8(3):e60049. doi: 10.1371/journal.pone.0060049. Epub 2013 Mar 29.
In this study, rat bone marrow stromal stem cells (BMSCs) were tracked after IV administration to rats with experimental stroke caused by middle cerebral artery occlusion (MCAO). In addition, the effects of BMSC treatment on blood cell composition, brain glia and sensorimotor behavior was studied and compared to that which occurred spontaneously during the normal recovery process after stroke. We found that the vast majority of radiolabeled or fluorescently labeled BMSCs traveled to and remained in peripheral organs (lungs, spleen, liver) 3 days after IV injection in the MCAO rat. Once in the circulation, BMSCs also produced rapid alterations in host blood cell composition, increasing both neutrophil and total white blood cell count by 6 hours post-injection. In contrast, few injected BMSCs traveled to the brain and almost none endured there long term. Nonetheless, BMSC treatment produced dramatic changes in the number and activation of brain astroglia and microglia, particularly in the region of the infarct. These cellular changes were correlated with a marked improvement in performance on tests of sensory and motor function as compared to the partial recovery of function seen in PBS-injected control rats. We conclude that the notable recovery in function observed after systemic administration of BMSCs to MCAO rats is likely due to the cellular changes in blood and/or brain cell number, activation state and their cytokine/growth factor products.
在这项研究中，通过静脉注射向大脑中动脉闭塞（MCAO）所致实验性中风大鼠体内追踪骨髓基质干细胞（BMSCs）。此外，还研究并比较了 BMSC 治疗对血细胞组成、脑胶质细胞和感觉运动行为的影响，与中风后正常恢复过程中自发发生的影响进行比较。我们发现，在 MCAO 大鼠静脉注射后 3 天，绝大多数放射性标记或荧光标记的 BMSCs 迁移到并保留在外周器官（肺、脾、肝）中。一旦进入循环，BMSCs 还会迅速改变宿主血细胞组成，在注射后 6 小时增加中性粒细胞和总白细胞计数。相比之下，很少有注射的 BMSCs 迁移到大脑中，几乎没有长期存在。尽管如此，BMSC 治疗还是会引起大脑星形胶质细胞和小胶质细胞数量和激活的显著变化，特别是在梗塞区域。这些细胞变化与感觉和运动功能测试中表现的显著改善相关，与 PBS 注射对照大鼠中观察到的部分功能恢复相比，功能改善明显。我们得出结论，在 MCAO 大鼠中全身给予 BMSC 后观察到的显著功能恢复可能是由于血液和/或脑细胞数量、激活状态及其细胞因子/生长因子产物的变化所致。
