HUMAN SAPHENOUS-VEIN ORGAN-CULTURE - A USEFUL MODEL OF INTIMAL HYPERPLASIA

Objectives: Although cell culture techniques and animal models of inti mal hyperplasia have increased our current understanding of the aetiol ogy of vein graft stenosis, the results of such studies have been diff icult to relate to the human situation. Design: The present study was designed to validate an organ culture of human saphenous vein by compa ring the changes occurring in cultured vein with those seen in patholo gical vein graft stenoses and to identify a suitable marker of cell pr oliferation. Materials and methods: Saphenous vein segments were cultu red for 14 days, fixed in formalin and processed for immunohistochemis try. Freshly excised stenoses were fixed and processed similarly. A nu mber of markers of cell proliferation were evaluated in the culture sy stem in order to identify the one best suited to this particular model . Results: Marked similarities were observed in the cellular and extra cellular matrix composition, and electron microscopy revealed that bot h the neointima of the cultured vein and the pathological lesion conta ined an abundance of smooth muscle cells of a secretory phenotype. Bro modeoxyuridine proved to be the most reliable proliferation marker and revealed that early proliferation in the superficial layers of the ve in intima gave rise to the formation of neointima. Both proliferation and neointimal thickness were maximal by day 14 in culture. Proliferat ion declined rapidly thereafter and the neointima was maintained. Conc lusions: The changes occurring in cultured vein and graft stenoses bor e many similarities, thereby justifying the use of organ culture as a valuable experimental tool.