Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia
Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia
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DOI：
10.1038/sj.jcbfm.9600527
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发表时间：
2008-02-01
影响因子：
6.3
通讯作者：
Kocsis, Jeffery D.
中科院分区：
文献类型：
--
作者：
Onda, Toshiyuki;Honmou, Osamu;Kocsis, Jeffery D.
从成人骨髓制备的人骨髓间充质干细胞(HMSCs)移植可改善大鼠脑动脉阻塞后的功能缺陷。尽管已经提出了几种解释这些治疗效果的假说，但目前的想法是，神经保护和血管生成都是主要原因。本研究比较了血管生成素-1基因修饰的人骨髓间充质干细胞(Ang-hMSCs)和血管生成素-1基因修饰的人骨髓间充质干细胞(Ang-hMSCs)对大鼠大脑中动脉永久性闭塞后6h的作用。磁共振成像和组织学分析显示，与对照组相比，接受hMSCs或Ang-hMSCs的大鼠大体病变体积有类似的缩小。尽管Ang-hMSC组和Ang-hMSC组均能改善缺血灶边缘附近的血管生成，但Ang-hMSC组某些边缘区域的新生血管和局部脑血流量更大。在跑台负荷试验中，hMSC组和Ang-hMSC组大鼠的功能恢复情况均优于对照组，但Ang-hMSC组效果更好。这些结果表明，静脉注射表达血管生成素的转基因hMSCs具有与hMSCs相似的缩小病变体积的效果，但Ang-hMSC组显示出病变边缘血管生成增加的增强区域，并在功能结果方面略有改善。
Transplantation of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Although several hypotheses to account for these therapeutic effects have been suggested, current thinking is that both neuroprotection and angiogenesis are primarily responsible. In this study, we compared the effects of hMSCs and angiopoietin-1 gene-modified hMSCs (Ang-hMSCs) intravenously infused into rats 6 h after permanent middle cerebral artery occlusion. Magnetic resonance imaging and histologic analyses revealed that rats receiving hMSCs or Ang-hMSCs exhibited comparable reduction in gross lesion volume as compared with the control group. Although both cell types indeed improved angiogenesis near the border of the ischemic lesions, neovascularization and regional cerebral blood flow were greater in some border areas in Ang-hMSC group. Both hMSC- and Ang-hMSC-treated rats showed greater improved functional recovery in the treadmill stress test than did control rats, but the Ang-hMSC group was greater. These results indicate the intravenous administration of genetically modified hMSCs to express angiopoietin has a similar effect on reducing lesion volume as hMSCs, but the Ang-hMSC group showed enhanced regions of increased angiogenesis at the lesion border, and modest additional improvement in functional outcome.