Chiba Shunmei, Ikeda Ritsuko, Kurokawa Manae S, Yoshikawa Hideshi, Takeno Mitsuhiro, Nagafuchi Hiroko, Tadokoro Mamoru, Sekino Hiroaki, Hashimoto Takuo, Suzuki Noboru
Department of Immunology, St. Marianna University School of Medicine, Kawasaki, Japan.
J Neurol Sci. 2004 Apr 15;219(1-2):107-17. doi: 10.1016/j.jns.2004.01.006.
We have treated undifferentiated mouse embryonic stem (ES) cells with all-trans retinoic acid (RA) to induce differentiation in vitro into neuron-like cells with good cell viability for use as a graft. Furthermore, we asked whether the RA-induced neuron-like cells restored neurological dysfunction. To this end, the cells were transplanted into right hemiplegia model of mice, developed by a cryogenic injury of motor cortex. Motor function of the recipients was gradually improved, whereas little improvement was observed in control mice. The lesion showed clustering of mature and almost mature neuron-like cells in mice transplanted with the RA-treated cells. The grafted cells had synaptic vesicles. This finding may suggest their maturation and synaptic connection in the recipient brain. Even though further study is necessary to elucidate molecular and cellular mechanisms responsible for the functional recovery, we consider that the ES cells may have advantage for use as a donor source in various neurological disorders including motor dysfunction.
我们用全反式维甲酸（RA）处理未分化的小鼠胚胎干细胞（ES细胞），以在体外诱导其分化为具有良好细胞活力的神经元样细胞，用作移植物。此外，我们还研究了RA诱导的神经元样细胞是否能恢复神经功能障碍。为此，将这些细胞移植到通过运动皮层低温损伤建立的小鼠右半身麻痹模型中。受体的运动功能逐渐改善，而对照小鼠几乎没有改善。在移植了经RA处理细胞的小鼠中，损伤部位显示出成熟和几乎成熟的神经元样细胞聚集。移植的细胞有突触小泡。这一发现可能表明它们在受体大脑中成熟并形成了突触连接。尽管需要进一步研究以阐明导致功能恢复的分子和细胞机制，但我们认为ES细胞在包括运动功能障碍在内的各种神经疾病中作为供体来源可能具有优势。
