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l-Carrageenan is a polysulphated carbohydrate that antagonises some heparin-binding growth factors. We assessed the effect of l-carrageenan on the proliferation of a panel of cell lines, some of which require heparin-binding growth factors for mitogenesis. The importance of growth factor antagonism for the anti-proliferative activity was also determined. Cell proliferation was determined by cell counts and a tetrazolium dye (MTT) assay, and DNA synthesis was determined by thymidine incorporation. The proliferation of the basic fibroblast growth factor (bFGF)-dependent endothelial cell line FBHE was inhibited by daily administration of l-carrageenan in a dose-dependent manner [concentration inhibiting cell growth by 50% (IC50 value), approx. 0.5 microgram/ml]. However, excess bFGF did not reverse the inhibitory effect. DNA synthesis was completely inhibited by concentrations of l-carrageenan that nonetheless allowed significant protein synthesis to occur. The proliferation of the androgen-dependent prostate-carcinoma cell line LNCaP was also inhibited by l-carrageenan (IC50 value, 5.5 micrograms/ml) and the cells were arrested at the G1/S boundary. l-Carrageenan inhibited DNA synthesis in MCF-7 cells stimulated by bFGF and transforming growth factor alpha (TGF alpha) but not in those stimulated by insulin-like growth factor 1 (IGF-1). Blocking IGF-1-mediated DNA synthesis with anti-IGF-1 receptor antibody alpha IR3 enhanced the inhibitory activity of l-carrageenan against MCF-7 cells grown in serum. A number of other transformed and non-transformed cell lines were either partially inhibited or not inhibited by l-carrageenan. l-Carrageenan had low anti-coagulant activity. l-Carrageenan is a selective anti-proliferative agent and warrants further investigation for anti-angiogenic therapy (in view of its activity against endothelial cells) and for the treatment of androgen-dependent prostate cancer.

Maintaining a proper pH level is crucial for successful cell culturing. Mammalian cells are commonly cultured in incubators, where the cell culture medium is saturated with a mixture of air and 5% carbon dioxide (CO2). Therefore, to keep cell culture medium pH in an acceptable level outside these incubators, a suitable CO2 concentration must be dissolved in the medium. However, it can be very difficult to control and measure precisely local concentration levels. Furthermore, possible undesired concentration gradients generated during long-term cell culturing are almost impossible to detect. Therefore, we have developed a computational model to estimate CO2 transport in silicone-based microfluidic devices. An extensive set of experiments was used to validate the finite element model. The model parameters were obtained using suitable measurement set-ups and the model was validated using a fully functional cell cultivation device. The predictions obtained by the simulations show very good responses to experiments. It is shown in this paper how the model helps to understand the dynamics of CO2 transport in silicone-based cell culturing devices possessing different geometries, thus providing cost-effective means for studying different device designs under a variety of experimental conditions without the need of actual testing. Finally, based on the results from the computational model, an alternative strategy for feeding CO2 is proposed to accelerate the system performance such that a faster and more uniform CO2 concentration response is achieved in the area of interest. acceptedVersion