Mori Taisuke, Kiyono Tohru, Imabayashi Hideaki, Takeda Yukiji, Tsuchiya Kohei, Miyoshi Shunichirou, Makino Hatsune, Matsumoto Kenji, Saito Hirohisa, Ogawa Satoshi, Sakamoto Michiie, Hata Jun-Ichi, Umezawa Akihiro
Department of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
Mol Cell Biol. 2005 Jun;25(12):5183-95. doi: 10.1128/MCB.25.12.5183-5195.2005.
Murine bone marrow stromal cells differentiate not only into mesodermal derivatives, such as osteocytes, chondrocytes, adipocytes, skeletal myocytes, and cardiomyocytes, but also into neuroectodermal cells in vitro. Human bone marrow stromal cells are easy to isolate but difficult to study because of their limited life span. To overcome this problem, we attempted to prolong the life span of bone marrow stromal cells and investigated whether bone marrow stromal cells modified with bmi-1, hTERT, E6, and E7 retained their differentiated capability, or multipotency. In this study, we demonstrated that the life span of bone marrow stromal cells derived from a 91-year-old donor could be extended and that the stromal cells with an extended life span differentiated into neuronal cells in vitro. We examined the neuronally differentiated cells morphologically, physiologically, and biologically and compared the gene profiles of undifferentiated and differentiated cells. The neuronally differentiated cells exhibited characteristics similar to those of midbrain neuronal progenitors. Thus, the results of this study support the possible use of autologous-cell graft systems to treat central nervous system diseases in geriatric patients.
小鼠骨髓基质细胞不仅能在体外分化为中胚层衍生物，如骨细胞、软骨细胞、脂肪细胞、骨骼肌细胞和心肌细胞，还能分化为神经外胚层细胞。人骨髓基质细胞易于分离，但由于其寿命有限，难以进行研究。为克服这一问题，我们试图延长骨髓基质细胞的寿命，并研究用bmi-1、hTERT、E6和E7修饰的骨髓基质细胞是否保留其分化能力或多能性。在本研究中，我们证明来自一名91岁供体的骨髓基质细胞的寿命可以延长，并且寿命延长的基质细胞在体外可分化为神经元细胞。我们从形态学、生理学和生物学方面检查了神经元分化细胞，并比较了未分化和分化细胞的基因谱。神经元分化细胞表现出与中脑神经元祖细胞相似的特征。因此，本研究结果支持自体细胞移植系统可能用于治疗老年患者中枢神经系统疾病。
