PHOTODYNAMIC THERAPY OF VASCULAR STENOSIS - RESULTS FROM CELL-CULTURE STUDIES ON HUMAN ENDOTHELIAL-CELLS

Background: Experimental results from human cell culture studies have shown that smooth muscle cells derived from human atherosclerotic plaques react more sensitively to photoactivated dihematoporphyrin-ester and -ether (DHE) than smooth muscle Cells from human nonatherosclerotic arteries. A therapeutic concept of photodynamic therapy of vascular stenosis appears, therefore, to be promising. The prerequisite for an intravascular application is a relatively harmless application of the photosensitizing agent to the luminal lining of endothelial cells. Methods: The effect of DHE with and without photoactivation was examined on endothelial cell cultures from human saphenous veins. The cellular uptake of DHE in relation to the serum content of the culture medium was evaluated, as well as its effect on proliferative activity, cell size, cell volume, and cellular viability. Results: Intracellular uptake of DHE decreased significantly when higher serum concentrations were present in the culture medium. Incubation of cells with the photosensitizer for 9 days in the dark without light activation resulted in a significant decrease of endothelial cell proliferation only at concentrations higher than 2.5 mug/mL (= 2.5 mg/kg body weight for systemic application in vivo). Additional photoactivation caused no reduction of cell viability at DHE concentrations of 1 mug/mL, but at 2.5 mug/mL and 5 mug/mL, a reduction of viable cells within 24 hours was observed in relation to the energy densities used for irradiation. Conclusions: Because smooth muscle cells from atherosclerotic plaques are, however, much more sensitive to photodynamic treatment, the concept of a photodynamic therapy of vascular stenosis may provide a good tool in the reduction of restenosis rates after recanalization of severely stenosed or even occluded arteries.