Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC

被引:365
作者
Guillot, Pascale V.
Gotherstrom, Cecilia
Chan, Jerry
Kurata, Hiroshi
Fisk, Nicholas M.
机构
[1] Imperial Coll London, Expt Fetal Med Grp, Inst Reprod & Dev Biol, London W12 0NN, England
[2] Queen Charlottes & Chelsea Hosp, Ctr Fetal Care, London, England
基金
英国医学研究理事会;
关键词
adult stem cells; telomere; telomerase; real-time reverse transcription-polymerase chain reaction mesenchymal stem cell; fetal stem cells;
D O I
10.1634/stemcells.20060208
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The biological properties of stem cells are key to the success of cell therapy, for which MSC are promising candidates. Although most therapeutic applications to date have used adult bone marrow MSC, increasing evidence suggests that MSC from neonatal and mid-gestational fetal tissues are more plastic and grow faster. Fetal stem cells have been isolated earlier in development, from first-trimester blood and hemopoietic organs, raising the question of whether they are biologically closer to embryonic stem cells and thus have advantages over adult bone marrow MSC. In this study, we show that human first-trimester fetal blood, liver, and bone marrow MSC but not adult MSC express the pluripotency stem cell markers Oct-4, Nanog, Rex-1, SSFA-3, SSEA-4, Tra-1-60, and Tra-1-81. In addition, fetal MSC, irrespective of source, had longer telomeres (p <.001), had greater telomerase activity (p <.01), and expressed more human telomerase reverse transcriptase (p <.01). Fetal MSC were also more readily expandable and senesced later in culture than their adult counterparts (p <.01). Compared with adult MSC, first-trimester fetal tissues constitute a source of MSC with characteristics that appear advantageous for cell therapy.
引用
收藏
页码:646 / 654
页数:9
相关论文
共 55 条
[1]   Maintenance of differentiation potential of human bone marrow mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene in despite of extensive proliferation [J].
Abdallah, BM ;
Haack-Sorensen, M ;
Burns, JS ;
Elsnab, B ;
Jakob, F ;
Hokland, P ;
Kassem, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 326 (03) :527-538
[2]   Stem cells in the kidney [J].
Al-Awqati, Q ;
Oliver, JA .
KIDNEY INTERNATIONAL, 2002, 61 (02) :387-395
[3]   3 MONOCLONAL-ANTIBODIES DEFINING DISTINCT DIFFERENTIATION ANTIGENS ASSOCIATED WITH DIFFERENT HIGH MOLECULAR-WEIGHT POLYPEPTIDES ON THE SURFACE OF HUMAN EMBRYONAL CARCINOMA-CELLS [J].
ANDREWS, PW ;
BANTING, G ;
DAMJANOV, I ;
ARNAUD, D ;
AVNER, P .
HYBRIDOMA, 1984, 3 (04) :347-361
[4]  
Anker PSI, 2003, HAEMATOLOGICA, V88, P845
[5]   Expression of transcription factor Oct-4 and other embryonic genes in CD133 positive cells from human umbilical cord blood [J].
Baal, N ;
Reisinger, K ;
Jahr, H ;
Bohle, RM ;
Liang, O ;
Münstedt, K ;
Rao, CV ;
Preissner, KT ;
Zygmunt, MT .
THROMBOSIS AND HAEMOSTASIS, 2004, 92 (04) :767-775
[6]   New developments in telomere length analysis [J].
Baird, DM .
EXPERIMENTAL GERONTOLOGY, 2005, 40 (05) :363-368
[7]   Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: Implications for their use in cell therapy [J].
Banfi, A ;
Muraglia, A ;
Dozin, B ;
Mastrogiacomo, M ;
Cancedda, R ;
Quarto, R .
EXPERIMENTAL HEMATOLOGY, 2000, 28 (06) :707-715
[8]   Replicative aging and gene expression in long-term cultures of human bone marrow stromal cells [J].
Banfi, A ;
Bianchi, G ;
Notaro, R ;
Luzzatto, L ;
Cancedda, R ;
Quarto, R .
TISSUE ENGINEERING, 2002, 8 (06) :901-910
[9]   Rex-1, a gene encoding a transcription factor expressed in rbe early embryo, is regulated via Oct-3/4 and Oct-6 binding to an Octamer site and a novel protein, Rox-1, binding to an adjacent site [J].
Ben-Shushan, E ;
Thompson, JR ;
Gudas, LJ ;
Bergman, Y .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (04) :1866-1878
[10]   Extension of life-span by introduction of telomerase into normal human cells [J].
Bodnar, AG ;
Ouellette, M ;
Frolkis, M ;
Holt, SE ;
Chiu, CP ;
Morin, GB ;
Harley, CB ;
Shay, JW ;
Lichtsteiner, S ;
Wright, WE .
SCIENCE, 1998, 279 (5349) :349-352