N012 Endovascular gingival fibroblast cell therapy reduced the size of aneurysms in a rabbit model of elastase-induced carotid injury

Abstract

Aortic abdominal aneurysm is characterized by excessive enlargement remodeling secondary to medial elastin destruction, and the severity of the disease has been correlated with metalloproteinase-9 (MMP-9). We aimed to evaluate whether embryo-like healing potential of a tissue (i.e., the gum) could be transposed to another tissue (i.e., the artery wall). Porcine pancreatic elastase was incubated during 15 minutes in rabbit carotid arteries (n=30). Four to 6 weeks later, carotid arteries were seeded endoluminally at the site of aneurysm with either rabbit gingival fibroblasts (n = 12) or culture medium only which served as control (n = 11). Vessel diameter and elastin density were assessed 4 weeks after cell therapy. Carotid diameter was similar before cell therapy in both group (3.4±0.5 mm vs 3.1 ± 0.37 mm, p=0.30). In contrast, carotid diameters were significantly decreased in aneurismal arteries seeded with rabbit gingival fibroblasts as compared to control aneurismal arteries (2.7 ± 0.64 mm vs 3.60 ± 0.52, p=0.003). Moreover, elastin density was significantly higher in the media after endovascular gingival fibroblast than in controls (32.5 ± 4.7 % vs 14.3 ± 8.2 %, p=0.001). Four weeks after cell transplantation, gingival fibroblasts inhibited MMP-9 secretion via a significant increase of its inhibitor, TIMP-1. Endovascular gingival fibroblast cell therapy improved elastin network and reduced the size of aneurysms in a rabbit model. This strategy may be attractive since gingival fibroblast are easily accessible are known to safely proliferate in culture medium.