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FGF-2 suppresses cellular senescence of human mesenchymal stem cells by down-regulation of TGF-beta2.

Ito T, Sawada R, Fujiwara Y, Seyama Y, Tsuchiya T

Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Tokyo 158-8501, Japan.

Human mesenchymal stem cells (hMSCs) are able to both self-replicate and differentiate into a variety of cell types. Fibroblast growth factor-2 (FGF-2) stimulates the growth of hMSCs in vitro, but its mechanisms have not been clarified yet. In this study, we investigated whether cellular senescence was involved in the stimulation of hMSCs growth by FGF-2 and the expression levels of transforming growth factor-beta1 and -beta2 (TGF-betas). Because hMSCs were induced cellular senescence due to long-term culture, FGF-2 decreased the percentage of senescent cells and suppressed G1 cell growth arrest through the suppression of p21(Cip1), p53, and p16(INK4a) mRNA expression levels. Furthermore, the levels of TGF-betas mRNA expression in hMSCs were increased by long-term culture, but FGF-2 suppressed the increase of TGF-beta2 mRNA expression due to long-term culture. These results suggest that FGF-2 suppresses the hMSCs cellular senescence dependent on the length of culture through down-regulation of TGF-beta2 expression.

Published 5 June 2007 in Biochem Biophys Res Commun, 359(1): 108-14.
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