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First published online August 11, 2005
Stem Cells Vol. 24 No. 1 January 2006, pp. 151 -167
doi:10.1634/stemcells.2004-0189; www.StemCells.com
© 2006 AlphaMed Press

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EMBRYONIC STEM CELLS-CHARACTERIZATION SERIES

Unique Gene Expression Signature by Human Embryonic Stem Cells Cultured Under Serum-Free Conditions Correlates with Their Enhanced and Prolonged Growth in an Undifferentiated Stage

Heli Skottmana,b, Anne-Marie Strömbergc, Eija Matilainenc, Jose Inzunzad, Outi Hovattab,c, Riitta Lahesmaaa

a Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland;
b REGEA, Institute for Regenerative Medicine, University of Tampere and Tampere University Hospital, Tampere, Finland;
c Department of Obstetrics and Gynecology, CLINTEC, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden;
d Department of Medical Nutrition, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden

Correspondence: Heli Skottman, Ph.D., REGEA Institute for Regenerative Medicine, University of Tampere and Tampere University Hospital, 33520 Tampere, Finland. Telephone: 358-3-3551-4119; Fax: 358-3-3551-8498; e-mail: Heli.Skottman{at}regea.fi

Understanding the interaction between human embryonic stem cells (hESCs) and their microenvironment is crucial for the propagation and the differentiation of hESCs for therapeutic applications. hESCs maintain their characteristics both in serum-containing and serum-replacement (SR) media. In this study, the effects of the serum-containing and SR culture media on the gene expression profiles of hESCs were examined. Although the expression of many known embryonic stem cell markers was similar in cells cultured in either media, surprisingly, 1,417 genes were found to be differentially expressed when hESCs cultured in serum-containing medium were compared with those cultured in SR medium. Several genes upregulated in cells cultured in SR medium suggested increased metabolism and proliferation rates in this medium, providing a possible explanation for the increased growth rate of nondifferentiated cells observed in SR culture conditions compared with that in serum medium. Several genes characteristic for cells with differentiated phenotype were expressed in cells cultured in serum-containing medium. Our data clearly indicate that the manipulation of hESC culture conditions causes phenotypic changes of the cells that were reflected also at the level of gene expression. Such changes may have fundamental importance for hESCs, and gene expression changes should be monitored as a part of cell culture optimization aiming at a clinical use of hESCs for cell transplantation.




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