Fibroblast growth factor-2 supports ex vivo expansion and maintenance of osteogenic precursors from human bone marrow.
We have investigated the effects of different growth factors on the proliferation and osteogenic potential of primary cultures of human bone marrow stromal cells (BMSC). Fibroblast growth factor (FGF)-2 was the most effective in promoting growth of these cells in vitro. The size of colonies formed in clonal conditions was approximately 2.5 times larger in presence of FGF-2. Also the morphology of BMSC was affected: cells cultured in 10% FCS alone became flattened, whereas FGF-2 expanded cells maintained a fibroblast-like elongated phenotype. Levels of alkaline phosphatase activity in BMSC expanded with FGF-2 were significantly lower (56%) than control and, after stimulation with ascorbic acid, betaGlycerophosphate and dexamethasone, FGF-2 expanded BMSC deposited approximately 3-fold more mineralized matrix than control cells. We have assessed osteogenicity of BMSC on hydroxyapatite porous scaffolds (bioceramics) by an ectopic bone formation assay. FGF-2 expanded BMSC yielded a higher bone formation (>20-fold) than control cells. We conclude that FGF-2, promoting BMSC proliferation, maintains cells in a more immature state allowing in vitro expansion of human osteo-progenitors which, associated with bioceramics, can differentiate in vivo and form bone tissue.
Martin
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I
Laboratorio di Differenziamento Cellulare, Istituto Nazionale per la Ricerca sul Cancro/Centro di Biotecnologie Avanzate, Genova, Italy.
Muraglia
A
A
Campanile
G
G
Cancedda
R
R
Quarto
R
R
D000328:Adult; D000469:Alkaline Phosphatase / Q000032:analysis; D001205:Ascorbic Acid / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D003907:Dexamethasone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005994:Glycerophosphates / Q000494:pharmacology; D013006:Growth Hormone / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D005994:Glycerophosphates; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D013006:Growth Hormone; D000469:Alkaline Phosphatase; D001205:Ascorbic Acid