Characterization of the chemotactic and mitogenic response of SMCs to PDGF-BB and FGF-2 in fibrin hydrogels.
The delivery of growth factors to cellularize biocompatible scaffolds like fibrin is a commonly used strategy in tissue engineering. We characterized smooth muscle cells (SMC) proliferation and chemotaxis in response to PDGF-BB and FGF-2, alone and in combination, in 2D culture and in 3D fibrin hydrogels. While both growth factors induced an equipotent mitogenic response in 2D culture, only FGF-2 was significantly mitogenic for SMCs in 3D culture. Only PDGF-BB was significantly chemotactic in a modified Boyden chamber assay. In a 3D assay of matrix invasion, both growth factors induced an invasive response into the fibrin hydrogel in both proliferating and nonproliferating, mitomycin C (MMC) treated cells. The invasive response was less attenuated by the inhibition of proliferation in PDGF-BB stimulated cells compared with FGF-2 stimulated cells. We conclude that SMCs cultured in fibrin hydrogels have a more robust chemotactic response to PDGF-BB compared with FGF-2, and that the response to FGF-2 is more dependent on cell proliferation. Delivery of both growth factors together potentiates the chemotactic, but not mitogenic response to either growth factor alone.
Ucuzian
Areck A
AA
Department of Surgery, Loyola University Medical Center, Maywood, Illinois, USA.
Brewster
Luke P
LP
East
Andrea T
AT
Pang
Yongang
Y
Gassman
Andrew A
AA
Greisler
Howard P
HP
D000818:Animals; D000077214:Becaplermin; D018929:Cell Culture Techniques; D002633:Chemotaxis / Q000187:drug effects*; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008934:Mitogens / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis
D020100:Hydrogels; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D005337:Fibrin