Maintenance of differentiation potential of human bone marrow mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene in despite of extensive proliferation

被引:218
作者
Abdallah, BM
Haack-Sorensen, M
Burns, JS
Elsnab, B
Jakob, F
Hokland, P
Kassem, M [1 ]
机构
[1] Odense Univ Hosp, Dept Endocrinol & Metab, KMEB, Mol Endocrinol Lab, DK-5000 Odense, Denmark
[2] Univ Wurzburg, Dept Orthopaed, D-97070 Wurzburg, Germany
[3] Aarhus Univ Hosp, Dept Hematol, DK-8000 Aarhus, Denmark
关键词
telomerase; stem cell; differentiation; proliferation; osteoblast;
D O I
10.1016/j.bbrc.2004.11.059
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human bone marrow mesenchymal stem cells (hMSC) represent a population of stem cells that are capable of differentiation into multiple lineages. However, these cells exhibit senescence-associated growth arrest and phenotypic changes during long-term in vitro culture. We have recently demonstrated that overexpression of human telomerase reverse transcriptase (hTERT) in hMSC reconstitutes telomerase activity and extends life span of the cells [Nat. Biotechnol. 20 (2002) 592]. In the present study, we have performed extensive characterization of three independent cell lines derived from the parental hMSC-TERT cell line based on different plating densities during expansion in culture: 1:2 (hMSC-TERT2), 1:4 (hMSC-TERT4), and 1:20 (hMSC-TERT20). The 3 cell lines exhibited differences in morphology and growth rates but they all maintained the characteristics of self-renewing stem cells and the ability to differentiate into multiple mesoderm-type cell lineages: osteoblasts, adipocytes, chondrocytes, and endothelial-like cells over a 3-year period in culture. Also, surface marker studies using flow cytometry showed a pattern similar to that known from normal hMSC. Thus, telomerization of hMSC by hTERT overexpression maintains the stem cell phenotype of hMSC and it may be a useful tool for obtaining enough number of cells with a stable phenotype for mechanistic studies of cell differentiation and for tissue engineering protocols. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:527 / 538
页数:12
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