Gene expression profiling of human mesenchymal stem cells for identification of novel markers in early- and late-stage cell culture.
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.
Division of Cellular and Gene Therapy Products, National Institute of Health Sciences, Tokyo 158-8501, Japan. stanabe@nihs.go.jp
Shihori
S
Tanabe
Yoji
Y
Sato
Takayoshi
T
Suzuki
Kazuhiro
K
Suzuki
Taku
T
Nagao
Teruhide
T
Yamaguchi
D017667:Adipocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D055514:Nephroblastoma Overexpressed Protein; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis
C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; C526319:CCN3 protein, human; C526320:Ccn3 protein, mouse; D050659:Core Binding Factor Alpha 1 Subunit; D005819:Genetic Markers; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C493709:RUNX2 protein, human; C069766:necdin; D055513:Connective Tissue Growth Factor