IN-VITRO STIMULATION OF HUMAN ENDOTHELIAL-CELLS BY DERIVATIZED DEXTRANS

Derivatized dextrans exert a stimulatory effect on the in vitro growth of human umbilical vein endothelial cells (HUVEC). Measurements of gr owth were monitored by [H-3]thymidine uptake and cell numbers. Our res ults show that some derivatized dextrans at 4 mug/ml (88 nM) increase the [H-3]thymidine incorporation, whereas starting dextran (40 000 Da) , dextran sulfate, and carboxymethyl dextran have no effect. In additi on, heparin under similar experimental conditions shows a slight inhib itory effect on the HUVEC growth. The stimulatory effect of derivatize d dextrans was also found when HUVEC grew during 7 days in medium cont aining 2% fetal bovine serum. We also observed that derivatized dextra ns had no effect on the mitogenic activity of acidic fibroblast growth factor, a mitogenic factor for several cell types including HUVEC. By assessment of [H-3]thymidine uptake at 48 h without serum, we conclud ed that the exogenous growth factors were not involved in the prolifer ative activity of these components. The stimulatory effects are relate d to the chemical nature and the proportion of substituents on the syn thetic polysaccharides. The data indicate that benzylamide sulfonated groups play a key role in the stimulation of HUVEC growth. Neither car boxyl nor sulfate groups alone exhibit this effect. Thus, the stimulat ory capacity of dextran derivatives depends strongly on the respective ratios of the functional groups.