Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
J Neurosci Res. 2009 Dec;87(16):3554-67. doi: 10.1002/jnr.22162.
The present study examined the effects of human umbilical cord blood-derived mesenchymal stem cells (HUCB-derived MSCs) delivered through the basilar artery in a canine thromboembolic brain ischemia model. Cerebral ischemia was induced through occlusion of the middle cerebral artery by injecting thrombus emboli into 10 beagles. In the HUCBC group (n = 5), 1 x 10(6) HUCB-derived MSCs were transplanted through the basilar artery 1 day after ischemic induction using an endovascular interventional approach. In the control group (n = 5), phosphate-buffered saline (PBS) was injected in the same manner in as the HUCBC group. Upon neurobehavioral examination, earlier recovery was observed in the HUCBC group. The HUCBC group showed a decrease in the infarction volume at 1 week after cerebral ischemic induction, whereas the control group showed an increase in the infarction volume at 1 week, by magnetic resonance image analysis. Transplanted cells had differentiated into neurons and astrocytes and were observed in and around endothelial cells that were positive for von Willebrand factor (vWF). HUCB-derived MSCs expressed neuroprotective factors, such as brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), at 4 weeks after the transplantation. The transplanted cells demonstrated their efficacy by reducing the infarction lesion volume and through earlier recovery from the neurological deficit. These results suggest that intraarterial transplantation of HUCB-derived MSCs could be useful in clinical treatment of cerebral ischemia.
本研究探讨了经基底动脉输注人脐带血源性间充质干细胞(HUCB 衍生 MSC)对犬血栓栓塞性脑缺血模型的影响。通过向 10 只比格犬大脑中动脉注射血栓栓塞物诱导脑缺血。在 HUCBC 组(n = 5)中,在缺血诱导后 1 天,通过血管内介入途径经基底动脉输注 1×10(6)个 HUCB 衍生 MSC。在对照组(n = 5)中,以与 HUCBC 组相同的方式注射磷酸盐缓冲盐水(PBS)。神经行为学检查发现,HUCBC 组恢复较早。磁共振成像分析显示,HUCBC 组在脑缺血诱导后 1 周时梗死体积减小,而对照组在 1 周时梗死体积增加。移植细胞已分化为神经元和星形胶质细胞,并在血管内皮细胞(von Willebrand 因子(vWF)阳性)中观察到。在移植后 4 周,HUCB 衍生 MSC 表达神经保护因子,如脑源性神经营养因子(BDNF)和血管内皮生长因子(VEGF)。移植细胞通过减少梗死病变体积和从神经功能缺损中更早恢复来证明其疗效。这些结果表明,经动脉内输注 HUCB 衍生 MSC 可能对治疗脑缺血有临床应用价值。