Endoluminal smooth muscle cell seeding limits intimal hyperplasia

Purpose: Intimal hyperplasia is one of the main responses of the vascular w all to injury. In the current study, we tested the hypothesis that endolumi nal seeding of host syngeneic vascular cells could limit intimal hyperplasi a induced by either mechanical deendothelialization or chronic allograft re jection in rat aorta. Methods. An experimental model of in situ seeding of syngeneic endothelial cells, smooth muscle cells (SMCs), and fibroblasts (FIBs) was used in mecha nically deendothelialized and allografted aortas. In a preliminary study, t he ability of the three cell types (n=5 per group) to seed on the deendothe lialized luminal surface of the aortic wall was evaluated after 2 days, wit h the use of fluorescent PKH as marker. In the first model, the abdominal a orta of Lewis rats was deendothelialized (n=6) or deendothelialized and see ded with either SMCs (n=6) or FIBs (n=6) before flow was restored. In the a llograft model, aortas were harvested from dark agouti rats and orthotopica lly grafted in Lewis receivers, directly (n=6) or after deendothelializatio n. Deendothelialization was performed alone (n=6) or associated with the se eding of similar host (Lewis) syngeneic SMCs (n=6) or FIBs (n=6). Results w ere evaluated at 2 months with histologic and morphometric methods. Results. SMCs and FIBs were able to adhere in situ to the deendothelialized aortic wall, whereas endothelial cells were not. In mechanically deendothe lialized aortas, the seeding of syngeneic SMCs led to a significant reducti on in intimal thickness compared with deendothelialized aortas or FIB-seede d aortas (26.9 +/-1.7 pm vs 55.5 +/-1.7 and 56.7 +/-1.7 mum, respectively), and a lower nuclear content (382.2 +/- 35.7 mum(2) vs 779.6 +/- 65.9 and 5 29.6 +/- 24.3 mum(2), respectively) of neointima. After SMC seeding, intima l hyperplasia was richer in elastin, whereas after FIB seeding it was riche r in collagen. In allografts, the seeding of syngeneic SMC led to a signifi cant reduction in intimal thickness compared with control aortas, deendothe lialized aortas, or FIB-seeded aortas (31.6 +/-1.1 mum vs 88.55 +/-2.8, 74. 6 +/-2.9, and 85.7 +/-2.6 mum, respectively), and a reduced nuclear content of the neointima (444.9 +/- 23.4 mum(2) vs 1529.1 +/- 116, 972.3 +/- 50, a nd 645.2 +/- 32.4 mum(2), respectively). Differences observed in the extrac ellular matrix composition were equivalent to those observed in the mechani cally deendothelialized model. Conclusions. Our results suggest that endoluminal seeding of syngeneic SMCs can be effective in reducing intimal hyperplasia both in a deendothelializ ation model and in arterial allografts. SMC and FIB endoluminal seeding led to a significatively different accumulation of extracellular matrix in the intima.