Modulation of human adventitial fibroblast function by photodynamic therapy of collagen matrix.

Abstract

Photodynamic therapy (PDT) is a promising strategy to limit restenosis. PDT depletes the resident cells from the vessel wall without adventitial cell ingrowth. This study was undertaken to further explore the mechanisms by which PDT of matrix acts on key mechanisms in the development of restenosis. Control and PDT-treated collagen type-I matrix gels were prepared. Thereafter, untreated human fibroblasts were seeded on matrix gels (n=12). Fibroblast proliferation and invasive migration were quantified by calibrated phase contrast microscopy. Fibroblast bFGF and TGF-beta1 mRNA expression were analyzed using a quantitative real-time reverse transcription polymerase chain reaction. Fibroblast proliferation on PDT-treated matrix gels was reduced by 30 and 76% after 3 and 7 days, respectively (3 days: P</=0.01, 7 days: P< or =0.001). PDT of matrix gels led to a 47% reduction of migration after 3 days and 51% after 7 days (P< or =0.001). PDT led to a 77% reduction of fibroblast TGF-beta1 mRNA (P< or =0.02) and to a 79% reduction of bFGF mRNA (P< or =0.03). PDT of matrix-induced reduction of bFGF and TGF-beta1 mRNA levels may be important mechanisms of reducing fibroblast proliferation and invasive migration and thus the development of restenosis. These newly identified mechanisms highlight PDT's pleiotropic effects on the vessel wall and its potential clinical value.