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Vol. 16, Issue 3, 1491-1499, March 2005
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* Department of Reproductive Biology and Pathology, Tokyo 157-8535, Japan;
Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;
Virology Division, National Cancer Center Research Institute, Tokyo, Japan; and
Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan
Submitted July 31, 2004;
Accepted December 20, 2004
Monitoring Editor: Lawrence Goldstein
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 p16INK4a/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 p16INK4a/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.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Akihiro Umezawa (umezawa{at}1985.jukuin.keio.ac.jp).
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