Growth factors stimulate neointimal cells in vitro and increase the thickness of the neointima formed at the neck of porcine aneurysms treated by embolization

Background and Purpose-Growth factors (GFs) techniques by stimulating neoin tima formation. Methods-Bilateral carotid aneurysms were constructed with venous pouches in 50 pigs and embolized intraoperatively with collagen sponges with and with out GFs (platelet-derived growth factor-BE [PDGF-BB] 0.15 or 1.5 mu g or tr ansforming growth factor-beta(1) [TGF-beta(1)] 60 or 600 ng) in each animal . DNA synthesis, cell proliferation, and collagen secretion assays were per formed to assess the in vitro effects of GFs on neointimal cells harvested from the treated aneurysms. I-125-PDGF-BB was used to study in vivo GF rele ase from sponges. The thickness of the neointima at the surface of the spon ges was measured 2 weeks after surgery. Since porcine aneurysms tend to hea l after collagen sponge embolization, this experiment was repeated in dogs, which have shown a propensity for recurrence with the same technique, with 600 ng TGF-beta(1) or platelet extracts. Results-PDGF-BB stimulated DNA synthesis and cell proliferation, while TGF- beta(1) strongly increased collagen synthesis of neointimal cells in vitro. Clearance of I-125-PDGF-BB from the sponges followed a biphasic curve, wit h 1.5% of exogenous PDGF-BB remaining at 1 week. The local delivery of PDGF -BB (0.15 or 1.5 mu g) and TGF-beta(1) (600 ng) significantly increased neo intimal thickness at the neck of porcine aneurysms, while 60 ng of TGF-beta (1) had no demonstrable effect. TGF-beta(1) (600 ng) or platelet extracts h ad no influence on canine aneurysms. Conchcsions-PDGF-BB and TGF-beta(1) can stimulate neointimal cells in vitro and neointima formation in vivo, but TGF-beta(1) and platelet extracts do not compensate for deficient thrombosis in canine aneurysms. Effects on the long-term results of embolization remain speculative.