Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia
Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia
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DOI：
10.1093/brain/awl207
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发表时间：
2006-10-01
期刊：
影响因子：
14.5
通讯作者：
Kocsis, J. D.
中科院分区：
文献类型：
--
作者：
Liu, H.;Honmou, O.;Kocsis, J. D.
静脉注射成人骨髓间充质干细胞（MSCs）可缩小脑梗死面积并改善大鼠脑缺血模型的功能缺陷。胎盘生长因子（PlGF）对受损的非神经组织具有血管生成作用。为了检验PlGF有助于MSC递送在脑缺血中的治疗益处的假设，我们比较了人MSC（hMSC）和用具有PlGF基因的纤维突变F/RGD腺病毒载体转染的hMSC（PlGF-hMSC）的全身递送的功效。采用微血管线栓法建立永久性大脑中动脉闭塞（MCAO）模型。MCAO后3 h，静脉注射hMSCs和PlGF-hMSCs。病变大小进行了评估，在3和6小时，1，3，4和7天使用MR成像和组织学。采用肢体放置试验和平板运动负荷试验评估功能结局。与对照假手术组相比，hMSC和PlGF-hMSC均减少了病变体积，诱导了血管生成并引起了功能改善，但PlGF-hMSC组的效果更大。酶联免疫吸附试验显示，在两个hMSC组中，梗死半球的PlGF增加，但PlGF-hMSC组增加更大。这些数据支持以下假设：PlGF有助于脑缺血中的神经保护和血管生成，并且可以通过静脉内递送hMSC来实现PlGF向脑的细胞递送。
Intravenous delivery of mesenchymal stem cells (MSCs) prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischaemia models. Placental growth factor (PlGF) is angiogenic to impaired non-neural tissue. To test the hypothesis that PlGF contributes to the therapeutic benefits of MSC delivery in cerebral ischaemia, we compared the efficacy of systemic delivery of human MSCs (hMSCs) and hMSCs transfected with a fibre-mutant F/RGD adenovirus vector with a PlGF gene (PlGF-hMSCs). A permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament. hMSCs and PlGF-hMSCs were intravenously injected into the rats 3 h after MCAO. Lesion size was assessed at 3 and 6 h, and 1, 3, 4 and 7 days using MR imaging and histology. Functional outcome was assessed using the limb placement test and the treadmill stress test. Both hMSCs and PlGF-hMSCs reduced lesion volume, induced angiogenesis and elicited functional improvement compared with the control sham group, but the effect was greater in the PlGF-hMSC group. Enzyme-linked immunosorbent assay of the infarcted hemisphere revealed an increase in PlGF in both hMSC groups, but a greater increase in the PlGF-hMSC group. These data support the hypothesis that PlGF contributes to neuroprotection and angiogenesis in cerebral ischaemia, and cellular delivery of PlGF to the brain can be achieved by intravenous delivery of hMSCs.