Combination of hTERT and bmi-1, E6, or E7 induces prolongation of the life span of bone marrow stromal cells from an elderly donor without affecting their neurogenic potential
Combination of hTERT and bmi-1, E6, or E7 induces prolongation of the life span of bone marrow stromal cells from an elderly donor without affecting their neurogenic potential
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DOI：
10.1128/mcb.25.12.5183-5195.2005
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发表时间：
2005-06-01
影响因子：
5.3
通讯作者：
Umezawa, A
中科院分区：
文献类型：
--
作者：
Mori, T;Kiyono, T;Umezawa, A
小鼠骨髓基质细胞在体外不仅可以分化为中胚层细胞，如骨细胞、软骨细胞、脂肪细胞、骨骼肌细胞、心肌细胞等，还可以分化为神经外胚层细胞。人骨髓基质细胞很容易分离，但由于其寿命有限，研究起来很困难。为了克服这个问题，我们试图延长骨髓基质细胞的寿命，并研究经Bmi-1、hTERT、E6和E7修饰的骨髓基质细胞是否保持其分化能力或多潜能。在这项研究中，我们证明了来自91岁捐赠者的骨髓基质细胞的寿命可以延长，并且延长了寿命的基质细胞在体外分化为神经细胞。我们对神经分化的细胞进行了形态、生理和生物学检查，并比较了未分化细胞和分化细胞的基因图谱。神经分化的细胞表现出与中脑神经前体细胞相似的特征。因此，这项研究的结果支持使用自体细胞移植系统治疗老年患者中枢神经系统疾病的可能性。
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.