Basic jibroblast growth factor (bFGF or FGF-2) is an angiogenic and pleiotropic growth factor involved in the proliferation and differentiation of numerous cell types. It is expressed mostly in tissues of mesoderm and neuroectoderm origin, and is thought to play an important role in the mesoderm induction. In recent years, a number of studies have identified fibroblast growth factors FGF-2 as key regulator of a variety of stem cell types.
The most common growth factors supplements for human embryonic stem cells culture media that promote self-renewal are fibroblast growth factor-2 (FGF-2), activin A, transforming growth factor b1 (TGFb1), and Wnt1 and 3. Although the majority of these growth factors are not necessary for culture of human embryonic stem cells with feeder cells or feeder cell-conditioned media, FGF-2 is required. This seems to be paradoxical because FGF-2 stimulates trophectoderm differentiation, the early stages of endodermal development, differentiation of endoderm-derived pancreatic cells, and differentiation of mesoderm-derived cardiovascular progenitors. One possible explanation is that FGF-2 has different effects on undifferentiated cells than cells that are already committed to differentiate.
Fgf2 exhibits positive and negative effects on growth and differentiation of mesenchymal stem cells. For example, Fgf2 has been shown to stimulate growth and preserve the differentiation potential of mesenchymal stem cells during long-term culture expansion in vitro. Alternatively, it has also been shown to promote osteoblast differentiation by inducing osteocalcin gene expression in mesenchymal stem cells and enhancing calcium deposition. Fgf2 also reportedly stimulates chondrogenic and adipogenic differentiation of human and rat mesenchymal stem cells, respectively. Recent studies by Debiais et al. revealed that Fgf2 exhibits differentiation stage-specific effects on cellular differentiation by showing that it stimulates growth of immature osteoblast progenitors but induces osteogenic differentiation of more mature precursors.
Although displaying a mild defective bone phenotype, FGF-2–knockout (KO) mice do not possess any observed deficits in steady-state hematopoiesis. However, several lines of evidence suggest that FGF-2 may have an active role in hematopoiesis. First, BM stromal cells from FGF-2 KO mice showed attenuated in vitro support of Hematopoietic Stem Cell maintenance. Second, FGFRs are present on the surface of long-term repopulating (LTR) murine CD34− Hematopoietic Stem Cells. Third, a chromosomal translocation mutation resulting in a constitutively active FGFR1 isoform was identified in some human myeloproliferative disorders. Last, an in vitro study showed that the addition of FGF-2 to prolonged BM cultures expands murine LTR-Hematopoietic Stem Cells. Studies also revealed that FGF signaling sustained and expanded Hematopoietic Stem Cells only in unfractionated BM cultures and not in sorted hematopoietic stem and progenitor cell cultures, suggesting an indirect effect mediated by the microenvironment.
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