Expression of the developmental markers STRO-1 and alkaline phosphatase incultures of human marrow stromal cells: Regulation by fibroblast growth factor (FGF)-2 and relationship to the expression of FGF receptors 1-4

Autologous marrow stromal cells have been proposed as an adjuvant In the tr eatment of bone defects and diseases. This will require the development of culture conditions that permit their rapid expansion ex vivo while retainin g their potential for further differentiation. Fibroblast growth factor (FG F)-2 has been proposed as a candidate for the ex vivo expansion of cells wi th enhanced osteogenic potential, and we have explored this possibility fur ther using cells obtained from a large cohort of adult human donors, Treatm ent with FGF-2 (0.001-2.5 ng/mL) had no detectable effect on colony formati on, but markedly increased their proliferative potential and that of their immediate progeny, as shown by the increases in colony size and cell number . Based on the observed increase in the expression of the developmental mar kers for the actions of FGF-2 appears to be more primitive cells of the ost eoblast lineage, and that, when added in combination with the synthetic glu cocorticoid dexamethasone (Dx), it interacts positively to promote further cell maturation. The maintenance of adequate levels of ascorbate was shown to he a critical component in determining nature of the effect of FGF-2 on AP expression. Variation in the response (predominantly in the magnitude an d/or sensitivity) of the cultured cell populations to treatment with FGF-2 was apparent, but a preliminary analysis indicated that this was not due to differences in the age or gender of the donors used. The cultured cell pop ulations were found to express multiple FGF receptors (FGFRs; 1-4) and the observed changes in the spectrum and abundance of FGFRs expressed in relati on to that of STRO-1 and AP are consistent with their expression being deve lopmentally regulated during: the process of osteogenic differentiation, Th ese results provide novel insights into the mechanism of FGF-2 on human cel ls of the osteoblast lineage and support the use of this factor, alone or i n combination with Dx, for the rapid, ex vivo expansion of cell populations with enhanced osteogenic potential. (C) 2000 by Elsevier Science Inc. All rights reserved.