Human saphenous vein organ culture: A useful model of intimal hyperplasia?

Objectives:Although cell culture techniques and animal models of intimal hyperplasia have increased our current understanding of the aetiology of vein graft stenosis, the results of such studies have been difficult to relate to the human situation.Design:The present study was designed to validate an organ culture of human saphenous vein by comparing the changes occurring in cultured vein with those seen in pathological vein graft stenoses and to identify a suitable marker of cell proliferation.Materials and methods:Saphenous vein segments were cultured for 14 days, fixed in formalin and processed for immunohistochemistry. Freshly excised stenoses were fixed and processed similarly. A number of markers of cell proliferation were evaluated in the culture system in order to identify the one best suited to this particular model.Results:Marked similarities were observed in the cellular and extracellular matrix composition, and electron microscopy revealed that both the neointima of the cultured vein and the pathological lesion contained an abundance of smooth muscle cells of a secretory phenotype. Bromodeoxyuridine proved to be the most reliable proliferation marker and revealed that early proliferation in the superficial layers of the vein intima gave rise to the formation of neointima. Both proliferation and neointimal thickness were maximal by day 14 in culture. Proliferation declined rapidly thereafter, and the neointima was maintained.Conclusions:The changes occurring in cultured vein and graft stenoses bore many similarities, thereby justifying the use of organ culture as a valuable experimental tool