Osteogenic stimulation of human adipose-derived stem cells by pre-treatment with fibroblast growth factor 2

Although adipose-derived stem cells (ADSCs) have many advantageous traits compared with other postnatal stem cells, the consensus is that their differentiation potential must be improved to allow their practical utilization. During the in vitro expansion of human ADSCs (hADSCs), pre-treatment of fibroblast growth factor 2 (FGF2) not only induced an increase of approximately 44-fold in cell number at passage 7 but also augmented the differentiation potential of hADSCs. The effect of FGF2-induced cell preconditioning was evaluated by in vitro and in vivo osteogenesis after pre-treatment with various concentrations of FGF2 (0, 5, 25 ng/ml). FGF2-pre-treated hADSCs showed enhanced in vitro osteogenesis. An evaluation of in vivo osteogenic potential with an ectopic bone model showed that FGF2-preconditioned hADSCs produced an abundant osteoid/bone matrix and the effect was dependent on the concentration of FGF2 pre-treatment; bone matrix formation by control hADSCs was virtually non-existent. FGF2-pre-treated hADSCs also showed enhanced in vitro chondrogenesis, whereas no significant difference was observed in adipogenic potential. Pre-treatment of hADSCs with FGF2 induced an increase in the expression of osteogenic markers such as Cbfa1/Runx2 and alkaline phosphatase and in the expression of β-catenin. These results suggest that FGF2 plays a highly beneficial role in the preconditioning of ADSCs for musculoskeletal tissue engineering.