Controlled release of stromal cell-derived factor-1α from silk fibroin-coated coils accelerates intra-aneurysmal organization and occlusion of neck remnant by recruiting endothelial progenitor cells

This study is to test the efficacy of stromal cell-derived factor-1 alpha (SDF-1 alpha)-coated coils together with endothelial progenitor cells (EPCs) transplantation in occluding aneurysms. Bone marrow-derived EPC surface markers were analyzed using flow cytometry. The migratory function of EPCs in response to SDF-1 alpha was evaluated using a modified Boyden chamber assay. Capillary-like tube formation was assessed using Matrigel gel. Coil morphologies before and after coating with SDF-1 alpha were observed under a scanning electron microscope. The level of SDF-1 alpha in supernatants was measured by ELISA. Sprague-Dawley rats were randomly allocated into five groups. Histological analysis was performed on days 14 and 28 after coil implantation. The bone marrow-EPCs could express CD133, CD34, and VEGFR-2 and form tubule-like structures in vitro. Migratory ability of EPCs in the presence of SDF-1 alpha-coated coils was similar to that in the presence of 5 ng/ml SDF-1 alpha gradient. Sustained release of SDF-1 alpha was achieved using silk fibroin as a carrier. In SDF-1 alpha-coated coils + EPCs transplantation group, a well-organized fibrous tissue bridging the orifice of aneurysms was shown on days 14 and 28. On day 28, tissue organization was greater in the SDF-1 alpha-coated coils group than in the unmodified coils group. Immunofluorescence showed a-smooth muscle actin-positive cells in organized tissue in sacs. Combined treatment with SDF-1 alpha-coated coils and EPCs transplantation is a safe and effective treatment for rat aneurysms. This may provide a new strategy for endovascular therapy following aneurysmal subarachnoid hemorrhage.