间充质干细胞
端粒酶逆转录酶
永生化细胞系
生物
端粒酶
细胞培养
细胞生物学
脂肪生成
细胞分化
干细胞
软骨发生
遗传学
基因
作者
Takeshi Okamoto,Tomoki Aoyama,Tomitaka Nakayama,Takeharu Nakamata,Taisuke Hosaka,Koichi Nishijo,Takashi Nakamura,Tohru Kiyono,Junya Toguchida
标识
DOI:10.1016/s0006-291x(02)00661-7
摘要
Mesenchymal stem cells (MSCs) are bone marrow stroma-derived cells, which can differentiate into several types of mesenchymal tissues. Although regarded as tissue-specific stem cells, human MSCs (hMSCs) have a low proliferative ability with a finite life span, which is a hurdle to further analysis of their biology. Here we attempted to establish immortalized hMSCs by retrovirus-mediated gene transfer. The gain in telomerase activity obtained on expression of human telomerase reverse transcriptase (hTERT) was found not to be enough to make the cell line immortal. A combination of hTERT with human papillomavirus E6 and E7 successfully immortalized hMSCs without affecting the potential for adipogenic, osteogenic, and chondrogenic differentiation. From the parental immortalized hMSC, 100 single-cell derived clones were established, of which the differentiation properties varied considerably, including tri-, bi-, and uni-directional clones, suggesting that hMSCs are constituted by a group of cells with different differentiation potential. These cell lines, being the first established immortalized clonal cell lines of hMSCs, could provide insights into the mechanisms regulating the early steps of differentiation from undifferentiated MSCs into a specific lineage.
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