Changes in expression of genes related to cell proliferation in human mesenchymal stem cells during in vitro culture in comparison with cancer cells.
We investigated the expression levels of several genes related to cell proliferation in human mesenchymal stem cells (hMSCs) during in vitro culture for use in clinical applications. In this study, we focused on the relationship between hMSC proliferation and transforming growth factor beta (TGFbeta) signaling during in vitro culture. The proliferation rate of hMSCs gradually decreased and marked changes in hMSC morphology were not observed in 3 months of in vitro culture. The mRNA expressions of TGFbeta1, TGFbeta2, and TGFbeta receptor type I (TGFbetaRI) in hMSCs increased with the length of cell culture. There had been no change in the TGFbeta3, TGFbetaRII, and TGFbetaRIII mRNA expressions by the 12th passage from the primary culture (at about 3 months). The mRNA expression of Smad3 increased, but those of c-myc and nucleostemin decreased with the length of hMSC in vitro culture. In addition, the expression profiles of the genes that regulate cellular proliferation in hMSCs were significantly different from those of cancer cells. In conclusion, hMSCs derived from bone marrow seldom underwent spontaneous transformation during 1-2 months of in vitro culture for use in clinical applications. In hMSCs as well as in epithelial cells, growth might be controlled by the TGFbeta family signaling.
Sawada
Rumi
R
Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. rsawada@nihs.go.jp
Ito
Tomomi
T
Tsuchiya
Toshie
T
D030201:Activin Receptors, Type I / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D005500:Follow-Up Studies; D015870:Gene Expression; D006367:HeLa Cells / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D053781:Transforming Growth Factor beta2 / Q000235:genetics; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I