title: Regulation of autocrine fibroblast growth factor-2 signaling by perfusion flow in 3D human mesenchymal stem cell constructs.
abstract: Perfusion bioreactor systems play a crucial role in mitigating nutrient limitation as well as providing biomechanical stimuli and redistributing regulatory macromolecules that influence human mesenchymal stem cells (hMSC) fate in three-dimensional (3D) scaffolds. As fibroblast growth factor-2 (FGF-2) is known to regulate hMSC phenotype, understanding the role of autocrine FGF-2 signaling in the 3D construct under the different perfusion flow provides important insight into an optimal bioreactor design. To investigate FGF-2 signaling inhibition in hMSC cultured in the porous poly(ethylene terephthalate) (PET) scaffolds perfused under two flow configurations, PD173074, an FGFR1 inhibitor, was added in growth media after 7 day of pre-culture and its impact on hMSC proliferation and clonogenicity during the subsequent 7 days of cultivation was analyzed. Compared with control constructs in growth media, the addition of PD173074 resulted in significant reduction in hMSC proliferation and colony formation in both constructs with a more dramatic reduction in the parallel flow constructs. The results demonstrate that autocrine FGF-2 plays a significant role in 3D scaffold and suggest modulation of the perfusion flow in the bioreactor as a strategy to influence autocrine actions and cell fate in the 3D scaffold.
authors: Dept of Chemical and Biomedical Engineering, Florida State University, Tallahassee, FL 32310, USA.
authors: Junho
authors: J
authors: Kim
authors: Teng
authors: T
authors: Ma
mesh_terms: D019898:Autocrine Communication; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010477:Perfusion; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D016222:Fibroblast Growth Factor 2