Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain
Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain
复制标题
DOI：
10.1038/jcbfm.2010.32
复制
发表时间：
2010-08-01
影响因子：
6.3
通讯作者：
Abe, Koji
中科院分区：
文献类型：
--
作者：
Kawai, Hiromi;Yamashita, Toru;Abe, Koji
中风是一种主要的神经系统疾病。诱导多能干细胞（iPS）可以从患者的任何部位产生，具有高繁殖能力和分化为各种类型细胞的多能性，这表明iPS细胞可以为细胞移植提供有希望的治疗。然而，将iPS细胞移植到缺血脑中还未见报道。在这项研究中，我们显示了iPS细胞在短暂性大脑中动脉闭塞（MCAO）小鼠模型中的命运。在短暂MCAO 30分钟后24小时，将未分化的iPS细胞（5 × 10（5））移植到同侧纹状体和皮质中。在细胞移植后28天进行行为学和组织学分析。令我们惊讶的是，移植的iPS细胞在缺血后的小鼠脑中扩增并形成比假手术脑中大得多的肿瘤。与MCAO+PBS（磷酸盐缓冲盐水）组相比，MCAO+iPS组的临床恢复延迟。iPS细胞可形成三胚层畸胎瘤，但在缺血区可提供大量Dcx阳性神经母细胞和少量成熟神经元。如果肿瘤发生得到适当控制，iPS细胞具有在缺血性脑损伤后提供神经细胞的有希望的潜力。Journal of Cerebral Blood Flow & Metabolism（2010）30，1487-1493; doi：10.1038/jcbfm.2010.32; 2010年3月10日在线发表
Stroke is a major neurologic disorder. Induced pluripotent stem (iPS) cells can be produced from basically any part of patients, with high reproduction ability and pluripotency to differentiate into various types of cells, suggesting that iPS cells can provide a hopeful therapy for cell transplantation. However, transplantation of iPS cells into ischemic brain has not been reported. In this study, we showed that the iPS cells fate in a mouse model of transient middle cerebral artery occlusion (MCAO). Undifferentiated iPS cells (5x10(5)) were transplanted into ipsilateral striatum and cortex at 24 h after 30 mins of transient MCAO. Behavioral and histologic analyses were performed at 28 day after the cell transplantation. To our surprise, the transplanted iPS cells expanded and formed much larger tumors in mice postischemic brain than in sham-operated brain. The clinical recovery of the MCAO+iPS group was delayed as compared with the MCAO+PBS (phosphate-buffered saline) group. iPS cells formed tridermal teratoma, but could supply a great number of Dcx-positive neuroblasts and a few mature neurons in the ischemic lesion. iPS cells have a promising potential to provide neural cells after ischemic brain injury, if tumorigenesis is properly controlled. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1487-1493; doi: 10.1038/jcbfm.2010.32; published online 10 March 2010