Healing mechanisms in experimental aneurysms. I. Vascular smooth muscle cells and neointima formation.

PURPOSE: The purpose of this work is to better define healing phenomena in this model, in an effort to find strategies to improve long term results of endovascular treatment.
METHODS: Lateral wall venous pouch aneurysms were constructed on both carotid arteries in 30 pigs. The aneurysms were packed with collagen sponges per-operatively in 25 animals. Angiography, serial histological studies and immuno-histochemistry tests were used to study healing phenomena and measure neointima formation at various time intervals from 1 day to 9 weeks after surgery. GDC embolization was performed in 5 other pigs for comparison with the collagen sponge model. Explants from the neointima at the neck of aneurysms as well as from the parent artery of 8 pigs were prepared in an attempt to grow and to characterize in vitro cells responsible for healing porcine aneurysms using immunocytochemistry and enzymatic assays. To confirm the hypothesis that an analogy exists between cells involved in aneurysmal healing and neointimal cells found in restenosis, explant outgrowths were scored and compared to explants from intact carotid arteries and carotid arteries subjected to angioplasty in 3 other animals. In addition, to test the value of neointima measurements in quantifying results, 6 dogs were analysed to correlate the thickness of the neointima formed at the neck of aneurysms with angiographic results in animals prone to recurrences.
RESULTS: Histopathological findings with collagen sponge packing were similar to the ones following coil embolization. Porcine aneurysms had a strong tendency to heal with a thick neointima primarily composed of vascular smooth muscle cells (VSMCs). Aneurysms in dogs did not heal as well and the neointima at the neck of treated lesions was thin. Cells responsible for healing of experimental porcine aneurysms could be cultured in vitro, and are activated VSMCs. These cells, similar to those harvested following balloon injury, had a higher colony forming capacity and an accelerated explant outgrowth rate as compared to cells derived from the parent artery.
CONCLUSION: Animals which heal poorly harbor a thin or deficient neointima at the neck of treated aneurysms. Favorable healing in porcine aneurysms involves VSMCs which form a thick neointima. These VSMCs can be cultured in vitro. They share similar outgrowth characteristics with VSMCs recovered after balloon angioplasty. The collagen sponge model may be useful to harvest cells for in vitro experimentation and in the in vivo evaluation of the local delivery of potential therapeutic molecules thought to improve healing following embolization of aneurysms.