Effect of a dextran derivative associated with TGF-beta1 or FGF-2 on dermal fibroblast behaviour in dermal equivalents.
Dextran derivatives that mimic the action of heparin have been shown to protect heparin-binding growth factors, such as Transforming Growth Factor-beta1 (TGF-beta1) and Fibroblast Growth Factor-2 (FGF-2). The aim of this study was to investigate the effect of LS21 DMCBSu, a dextran derivative which contains methylcarboxylate, benzylamide and sulfate groups, both by itself and when combined with TGF-beta1 and FGF-2, on the behaviour of fibroblasts. Two systems were assessed: a monolayer culture and three-dimensional collagenous matrices (dermal equivalent). Polymeric biomaterial LS21 DMCBSu and LS21 DMCBSu associated with either TGF-beta1 or FGF-2, were added to the monolayer culture on day 3. After 7 days of culture the number of cells was determined. Two treatments were carried out on the dermal equivalents: 9 days of treatment from day 0 to day 9 of culture and 9 days of treatment from day 21 to day 30 of culture for the premature and the mature dermal equivalents respectively. In the monolayer culture, the bioactive polymer produced a slight increase in fibroblast growth (10% with 10 microg/ml of LS21 DMCBSu) and promoted the stimulating effect of the growth factors on cell growth. In the premature dermal equivalents growth was stimulated by 20% when 10 microg/ml LS21 DMCBSu was added. The dextran derivative mixed with TGF-beta1 slightly inhibited the growth effect of the growth factor in the dermal equivalents. The functionalized dextran with FGF-2 enhanced the stimulating effect of the growth factor in the premature dermal equivalent. A significant increase in cell growth was observed with the fibroblasts treated with the FGF-2 LS21 DMCBSu mixture and FGF-2 (51% and 40%, respectively). However, none of the described treatments affected the cell growth in the mature dermal equivalent. Furthermore, the dextran derivative had no effect on dermal contraction under these experimental conditions (3D culture).
Frank
Laetitia
L
Laboratoire de Recherches sur les Macromolécules, CNRS FRE 2314, Université Paris 13, 93430 Villetaneuse, France. laetitia.frank@free.fr
Lebreton-Decoster
Corinne
C
Godeau
Gaston
G
Coulomb
Bernard
B
Jozefonvicz
Jacqueline
J
D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D020405:Dermis / Q000166:cytology* / Q000187:drug effects*; D003911:Dextrans / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts; D006801:Humans; D008297:Male; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D003911:Dextrans; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D003094:Collagen