In vitro stimulation of human endothelial cells by derivatized dextrans

Abstract

Derivatized dextrans exert a stimulatory effect on the in vitro growth of human umbilical vein endothelial cells (HUVEC). Measurements of growth were monitored by [3H]thymidine uptake and cell numbers. Our results show that some derivatized dextrans at 4 micrograms/ml (88 nM) increase the [3H]thymidine incorporation, whereas starting dextran (40,000 Da), dextran sulfate, and carboxymethyl dextran have no effect. In addition, heparin under similar experimental conditions shows a slight inhibitory effect on the HUVEC growth. The stimulatory effect of derivatized dextrans was also found when HUVEC grew during 7 days in medium containing 2% fetal bovine serum. We also observed that derivatized dextrans had no effect on the mitogenic activity of acidic fibroblast growth factor, a mitogenic factor for several cell types including HUVEC. By assessment of [3H]thymidine uptake at 48 h without serum, we concluded that the exogenous growth factors were not involved in the proliferative activity of these components. The stimulatory effects are related to the chemical nature and the proportion of substituents on the synthetic polysaccharides. The data indicate that benzylamide sulfonated groups play a key role in the stimulation of HUVEC growth. Neither carboxyl nor sulfate groups alone exhibit this effect. Thus, the stimulatory capacity of dextran derivatives depends strongly on the respective ratios of the functional groups.

Liposomes coated with chemically modified dextran interact with human endothelial cells

“…2 For the purpose of this study, dextran was chosen because this polysaccharide (a) stabilizes liposomes, 15,26 (b) increases the circulatory half-life of liposomes, 31 (c) reduces protein adsorption, 11 (d) is a good macromolecular drug carrier, 32,33 and (e) can be functionalized to endow various biologic properties. [17][18][19][20][21][22][23] Here, we compared the uptake by human endothelial cells of conventional liposomes and dextran-or functionalized dextrancoated liposomes using radioactive and fluorescent lipid probes. The polysaccharides were inserted during the liposome formation within the liposome membrane through a cholesterol moiety which acts as a hydrophobic anchor.…”

“…1) have been shown to exhibit heparin-like properties, such as anticoagulation capacities, 18 inhibition of smooth-muscle cell growth, 19 antiviral activities, 20,21 and anticomplementary activity in vitro and in vivo. 22 Functionalized dextrans (FDx) were also found to interact with human umbilical vein endothelial cells, 23 depending on the degree of substitution of specific chemical groups. In this study, the uptake by human endothelial cells of liposomes coated with dextran or FDx was investigated.…”

Bioactive specific biomaterials: Present and future

“…The effect on mitogenesis of HUVEC in the absence of serum leads t o the conclusion that exogenous growth factors are not involved in the proliferative capacity of these materials (ref. 11 1. It appears that benzylamide sulfonate groups play an important role in the stimulation of HUVEC.…”

Antiproliferative polysaccharides modulate distribution and phenotypic expression of collagens by gingival fibroblasts

“…[11][12][13] At the cellular level, we have demonstrated that CMDBS was able to mimic heparin and regulate proliferation of different types of cells. [14][15][16] Independently of cell proliferation regulation, we have shown that CMDBS could significantly modulate the expression of collagen biosynthesis in vascular cells. 17,18 General laws seem to sustain wound healing or tissue repair, whatever the nature and location of the injured tissue.…”