Toyama Kentaro, Honmou Osamu, Harada Kuniaki, Suzuki Junpei, Houkin Kiyohiro, Hamada Hirofumi, Kocsis Jeffery D
Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
Exp Neurol. 2009 Mar;216(1):47-55. doi: 10.1016/j.expneurol.2008.11.010. Epub 2008 Nov 27.
Intravenous transplantation of human mesenchymal stem cells (hMSCs) expanded from adult bone marrow ameliorates functional deficits in rat cerebral infarction models. Several hypotheses to account for the therapeutic mechanisms have been suggested, but angiogenesis is thought to be of critical importance. Recently, we have reported the therapeutic benefits of hMSCs which have been transfected with the angiopoietin-1 gene in a rat permanent middle cerebral artery occlusion (MCAO) model. To potentially enhance the therapeutic effects of angiopoietin-1 gene-modified hMSC (Ang-hMSC), we transfected hMSCs with the angiopoietin-1 gene and the VEGF gene, and investigated whether the combination of Ang-1 and VEGF gene-modified hMSCs (Ang-VEGF-hMSC) contribute to functional recovery in a rat MCAO model. We induced MCAO using intraluminal vascular occlusion, and hMSCs, Ang-hMSCs, VEGF-hMSCs or Ang-VEGF-hMSCs were intravenously infused 6 h later. MRI and behavioral analyses revealed that rats receiving Ang-VEGF-hMSCs showed the greatest structural-functional recovery as compared to the other groups. These results suggest that intravenous administration of hMSCs transfected with the angiopoietin-1 and VEGF gene using a fiber-mutant adenovirus vector may represent a new strategy for the treatment of ischemia.
从成人骨髓中扩增的人间充质干细胞（hMSCs）静脉移植可改善大鼠脑梗死模型中的功能缺陷。已经提出了几种解释治疗机制的假说，但血管生成被认为至关重要。最近，我们报道了在大鼠永久性大脑中动脉闭塞（MCAO）模型中，用血管生成素-1基因转染的hMSCs的治疗益处。为了潜在地增强血管生成素-1基因修饰的hMSC（Ang-hMSC）的治疗效果，我们用血管生成素-1基因和VEGF基因转染hMSCs，并研究Ang-1和VEGF基因修饰的hMSCs（Ang-VEGF-hMSC）的组合是否有助于大鼠MCAO模型的功能恢复。我们使用腔内血管闭塞诱导MCAO，并在6小时后静脉注射hMSCs、Ang-hMSCs、VEGF-hMSCs或Ang-VEGF-hMSCs。MRI和行为分析显示，与其他组相比，接受Ang-VEGF-hMSCs的大鼠表现出最大的结构-功能恢复。这些结果表明，使用纤维突变腺病毒载体静脉注射用血管生成素-1和VEGF基因转染的hMSCs可能代表一种治疗缺血的新策略。
