Synthesis of novel celluloses derivatives and investigation of their mitogenic activity in the presence and absence of FGF2.

Abstract

Novel cellulose sulfates (CS) with a controlled degree of sulfation (DS(S)) were synthesized through acetosulfation as well as direct sulfation. CS containing carboxyl (CO) or carboxymethyl (CM) groups were prepared by TEMPO oxidation or by carboxymethylation with chloroacetic acid. The derivatization was characterized by nuclear magnetic resonance and Raman spectroscopy. The derivatives were investigated regarding their cytotoxicity and mitogenic activity by modulation of 3T3 fibroblast proliferation with or without exogenous FGF2. All derivatives were non-toxic for 3T3 cells. CS strongly promoted FGF2-induced proliferation, which was positively related to overall DS(S). In the absence of FGF2, minute quantities of CS with intermediate degrees of sulfation exerted stronger mitogenic effects than heparin. No significant promoting effects of CO and CM on cell proliferation were found, though the structure of CO shows similarities to heparin.