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Journal of Biochemistry Advance Access originally published online on June 11, 2008
Journal of Biochemistry 2008 144(3):399-408; doi:10.1093/jb/mvn082
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© 2008 The Japanese Biochemical Society

Gene Expression Profiling of Human Mesenchymal Stem Cells for Identification of Novel Markers in Early- and Late-Stage Cell Culture

Shihori Tanabe*, Yoji Sato, Takayoshi Suzuki, Kazuhiro Suzuki, Taku Nagao and Teruhide Yamaguchi#

Division of Cellular and Gene Therapy Products, National Institute of Health Sciences, Tokyo 158-8501, Japan

*To whom correspondence should be addressed. Tel: +81-3-3700-1141, Fax: +81-3-3700-9217, E-mail: stanabe{at}nihs.go.jp

Received January 9, 2008; Accepted June 5, 2008


  Abstract

Human mesenchymal stem cells (hMSCs) are multipotent cells that differentiate into several cell types, and are expected to be a useful tool for cellular therapy. Although the hMSCs differentiate into osteogenic cells during early to middle stages, this differentiation capacity decreases during the late stages of cell culture. To test a hypothesis that there are biomarkers indicating the differentiation potential of hMSCs, we performed microarray analyses and profiled the gene expression in six batches of hMSCs (passages 4–28). At least four genes [necdin homolog (mouse) (NDN), EPH receptor A5 (EPHA5), nephroblastoma overexpressed gene (NOV) and runt-related transcription factor 2 (RUNX2)] were identified correlating with the passage numbers in all six batches. The results showed that the osteogenic differentiation capacity of hMSCs is down-regulated in the late stages of cell culture. It seemed that adipogenic differentiation capacity was also down-regulated in late stage of the culture. The cells in late stage are oligopotent and the genes identified in this study have the potential to act as quality-control markers of the osteogenic differentiation capacity of hMSCs.

Key Words: cellular therapy, culture stage marker, differentiation, gene expression, stem cell

Abbreviations: EPHA5, EPH receptor A5; hMSCs, human mesenchymal stem cells; NDN, necdin homolog (mouse); NOV, nephroblastoma overexpressed gene; PBS, phosphate buffered saline; RUNX2, runt-related transcription factor 2

#Present address: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences


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