Fibroblast Growth Factor Ligand Dependent Proliferation and Chondrogenic Differentiation of Synovium-Derived Stem Cells and Concomitant Adaptation of Wnt/Mitogen-Activated Protein Kinase Signals

Cell expansion techniques commonly utilize exogenous factors to increase cell proliferation and create a larger cell population for use in cell-based therapies. One strategy for cartilage regenerative therapies is autologous stem cell expansion and fibroblast growth factor (FGF) supplementation during cell expansion, particularly FGF-2. However, it is unknown whether FGF-10, another FGF implicated in limb and skeletal development, can elicit the same rejuvenation responses in terms of proliferation and differentiation of human synovium-derived stem cells (SDSCs). In this study, we expanded SDSCs in either FGF-2 or FGF-10 for 7 days; a control group had no treatment. FGF-2 and FGF-10 supplementation was also exclusively tested during the differentiation phase. Expanded SDSCs were evaluated for their ability to successfully engage in chondrogenic and osteogenic differentiation. We found that FGF-2 supplementation during proliferation, but not differentiation, was able to increase glycosaminoglycan deposition, pellet size, and chondrogenic gene expression following chondrogenic induction, as well as increased calcium deposition, alkaline phosphatase activity, and expression of vital osteogenic differentiation genes following osteogenic induction. FGF-10 did not elicit a similar preconditioning effect. We also observed changes of both Wnt signals and mitogen-activated protein kinase expression during SDSC chondrogenesis, which occurred in a manner dependent upon the supplementation phase of FGF-2 administration. These results indicated that FGF-2, but not FGF-10, may be supplemented during stem cell expansion to prime cells for successful chondrogenesis and osteogenesis.