Immortalization of human fetal cells:: The life span of umbilical cord blood-derived cells can be prolonged without manipulating p16INK4a/RB braking pathway
Immortalization of human fetal cells:: The life span of umbilical cord blood-derived cells can be prolonged without manipulating p16INK4a/RB braking pathway
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DOI：
10.1091/mbc.e04-07-0652
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Kiyono, T
中科院分区：
文献类型：
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作者：
Terai, M;Uyama, T;Kiyono, T
人脐带血来源的间充质干细胞（UCBMSCs）有望成为骨髓来源的间充质干细胞的良好替代品。然而，由于它们的寿命有限，很难对其进行研究。为了克服这个问题，我们试图产生一种具有长寿命的UCBMSCs菌株，并研究该菌株是否可以在体外保持表型。用携带人端粒酶逆转录酶（human telomerase reverse transcriptase，hTERT）的逆转录病毒感染脐血间充质干细胞以延长其寿命。UCBMSC经历30次群体倍增（PD），并在PD 37时停止分裂。用hTERT新建立的UCBMSCs（UCBTERTs）增殖>120 PD。p16（INK 4a）/RB制动通路导致衰老可以通过引入Bmi-1（polycomb-group基因）和人乳头瘤病毒16型E7来抑制，但是用hTERT延长UCBMSCs的寿命不需要抑制p16（INK 1a）/RB通路。UCBTERTs的特征在寿命延长期间保持不变。UCBTERTs为进一步研究细胞衰老和将来应用于使用脐带血细胞的基于细胞的治疗提供了强有力的模型。
Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to serve as an excellent alternative to bone marrow-derived human mesenchymal stem cells. However, it is difficult to study them because of their limited life span. To overcome this problem, we attempted to produce a strain of UCBMSCs with a long life span and to investigate whether the strain could maintain phenotypes in vitro. UCBMSCs were infected with retrovirus carrying the human telomerase reverse transcriptase (hTERT) to prolong their life span. The UCBMSCs underwent 30 population doublings (PDs) and stopped dividing at PD 37. The UCBMSCs newly established with hTERT (UCBTERTs) proliferated for >120 PDs. The p16(INK4a)/RB braking pathway leading to senescence can be inhibited by introduction of Bmi-1, a polycomb-group gene, and human papillomavirus type 16 E7, but the extension of the life span of the UCBMSCs with hTERT did not require inhibition of the p16(INK1a)/RB pathway. The characteristics of the UCBTERTs remained unchanged during the prolongation of life span. UCBTERTs provide a powerful model for further study of cellular senescence and for future application to cell-based therapy by using umbilical cord blood cells.