Transplantation of neuronal cells induced from human mesenchymal stem cells improves neurological functions after stroke without cell fusion
Transplantation of neuronal cells induced from human mesenchymal stem cells improves neurological functions after stroke without cell fusion
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DOI：
10.1002/jnr.22501
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发表时间：
2010-12
影响因子：
4.2
通讯作者：
Haiyan Xu;K. Miki;S. Ishibashi;J. Inoue;Liyuan Sun;S. Endo;I. Sekiya;T. Muneta;J. Inazawa;M. Dezawa;H. Mizusawa
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文献类型：
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作者：
Haiyan Xu;K. Miki;S. Ishibashi;J. Inoue;Liyuan Sun;S. Endo;I. Sekiya;T. Muneta;J. Inazawa;M. Dezawa;H. Mizusawa
治疗中风的选择有限，但干细胞具有多能性，有望成为一种治疗方法。骨髓间充质干细胞(MSC)来源的神经细胞比MSCs具有更好的治疗效果。为了阐明神经细胞的治疗机制，我们采用沙土鼠左侧颈总动脉结扎的方法建立了局灶性脑梗塞模型。我们将Notch胞内区基因导入人骨髓间充质干细胞(HMSCs)，诱导其分化为神经细胞(hn-MSCs)。阻断后4天将这些细胞立体定向移植到局部缺血区。移植后28d进行行为学分析，然后进行荧光原位杂交(FISH)和组织学评价。移植细胞分布于梗死灶周围，HN-MSCs和hMSCs分别存活约8.5%和4.2%，HN-MSCs中微管相关蛋白2+(MAP-2+)和突起的比例为53.2%±9.6%，hMSCs中MAP-2+的比例仅为0.9%±0.3%。在FISH中，在hN-MSCs和hMSCs移植的脑中都检测到了人核特异性信号，但没有移植细胞具有合并的沙土鼠特异性核信号。移植HN-MSC的动物在T迷宫、双侧不对称和旷场测试中表现出明显好于对照组的恢复。这些发现表明，hN-MSCs比hMSCs对卒中有更大的治疗潜力，细胞融合不是MSC移植的主要治疗机制。©2010 Wiley-Liss公司。
The options for treating stroke are limited, but stem cells hold promise as a therapy because of their multipotency. Neuronal cells derived from mesenchymal stem cells (MSC) were reported to have more therapeutic effect than MSCs. For elucidating the therapeutic mechanism of neuronal cells, here we generated a model of focal cerebral infarction by performing left common carotid artery occlusion in adult gerbils. We transfected human trabecular bone‐derived MSCs (hMSCs) with the Notch intracellular domain to induce their differentiation into neuronal cells (hN‐MSCs). These cells were stereotaxically transplanted into the local ischemic hemisphere 4 days after the occlusion. Behavioral analyses were conducted 28 days after transplantation, and then fluorescence in situ hybridization (FISH) and a histological evaluation were performed. Histologically, transplanted cells were distributed around the periinfarct region, and approximately 8.5% and 4.2% of hN‐MSCs and hMSCs survived, respectively; 53.2% ± 9.6% of hN‐MSCs were microtubule‐associated protein 2+ (MAP‐2+) and extended neurites, whereas only 0.9% ± 0.3% of hMSCs were MAP‐2+. In FISH, human nucleus‐specific signals were detected in both hN‐MSCs and hMSCs grafted brains, but no transplanted cell had a merged gerbil‐specific nuclear signals. hN‐MSC‐transplanted animals showed significantly better recovery than animals given control vehicle in the T‐maze, bilateral asymmetry, and open field tests. These findings suggested that hN‐MSCs have greater therapeutic potential than hMSCs for stroke and that cell fusion does not primarily contribute to the therapeutic mechanism of MSC transplantation. © 2010 Wiley‐Liss, Inc.