Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
J Cereb Blood Flow Metab. 2010 Aug;30(8):1487-93. doi: 10.1038/jcbfm.2010.32. Epub 2010 Mar 10.
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 (5 x 10(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.
中风是一种主要的神经紊乱疾病。诱导多能干细胞（iPS 细胞）可以从患者的任何基本部位产生，具有高繁殖能力和多能性，可分化为多种类型的细胞，这表明 iPS 细胞可为细胞移植提供有希望的治疗方法。然而，尚未有报道将 iPS 细胞移植到缺血性大脑中。在这项研究中，我们展示了 iPS 细胞在短暂性大脑中动脉闭塞（MCAO）小鼠模型中的命运。在短暂性 MCAO 后 30 分钟，将未分化的 iPS 细胞（5 x 10(5)）移植到同侧纹状体和皮质中。在细胞移植后 28 天进行行为和组织学分析。令我们惊讶的是，与假手术组相比，移植到缺血性脑内的 iPS 细胞在小鼠中扩增并形成了比 sham 操作组更大的肿瘤。与 MCAO+PBS（磷酸盐缓冲盐水）组相比，MCAO+iPS 组的临床恢复延迟。iPS 细胞形成三胚层畸胎瘤，但可在缺血性病变中提供大量 Dcx 阳性神经母细胞和少量成熟神经元。如果能够适当控制肿瘤形成，iPS 细胞在缺血性脑损伤后有提供神经细胞的巨大潜力。
