Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF

Mesenchymal stem cells (MSC) that can differentiate to various connective t issue cells may be useful for autologous cell transplantation to defects of bone, cartilage, and tendon, if MSC can be expanded in vitro. However, a s hort life span of MSC and a reduction in their differentiation potential in culture have limited their clinical application. The purpose of this study is to identify a growth factor(s) involved in self-renewal of MSC and the maintenance of their multilineage differentiation potential. Fibroblast gro wth factor-2 (FGF-2) markedly increased the growth rate and the life span o f rabbit, canine, and human bone marrow MSC in monolayer cultures. This eff ect of FGF-2 was more prominent in low-density cultures than in high-densit y cultures. In addition, all MSC expanded in vitro with FGF-2, but not with out FGF-2, differentiated to chondrocytes in pellet cultures. The FGF(+) MS C also retained the osteogenic and adipogenic potential throughout many mit otic divisions. These findings suggest that FGFs play a crucial role in sel f-renewal of MSC. (C) 2001 Academic Press.