Endovascular treatment of experimental aneurysms by use of biologically modified embolic devices: Coil-mediated intraaneurysmal delivery of fibroblast tissue allografts

BACKGROUND AND PURPOSE: Our long-term goal is to improve intraaneurysmal fi brosis after aneurysm embolization, by implanting exogenous fibroblasts, us ing platinum coils. For the current project, we tested two hypotheses: 1) t hat exogenous, fluorescence-labeled rabbit fibroblast allografts remained v iable and proliferated within rabbit carotid arteries, and 2) that these fi broblast allografts could be reliably implanted into experimental aneurysms by use of platinum coils. METHODS: Part 1. New Zealand White rabbit synovial fibroblasts obtained fro m a commercial vender were labeled with a fluorescent membrane marker. The common carotid arteries of New Zealand White rabbits were surgically expose d, ligated proximally and distally, and entered with 22-g angiocatheters, T hrough the angiocatheter we injected either phosphate-buffered saline-conta ining fluorescence-labeled fibroblasts (treatment vessels) or saline only ( control vessels). The wounds were closed, and the subjects were kept alive for various time points up to 2 weeks. After sacrifice, the carotid artery segments were resected, processed for frozen-section histologic examination , and evaluated using epifluorescent microscopy and hematoxylin and eosin s taining. Cell viability and proliferation were determined by comparing the treatment versus control vessels. Part 2. A) Fluorescence-labeled cells were grown in culture on platinum coi ls, which were then exposed to systemic arterial flow in the rabbit thoraci c aorta for various lengths of time up to 40 minutes. The coil segments wer e then examined using fluorescent microscopy and the presence and relative amount of cells remaining on the coil were documented. B) Experimental aneurysms in rabbits were embolized with control platinum c oils (n = 9) and platinum coils bearing rabbit synovial fibroblasts that we re grown onto the coils in culture prior to implantation (n = 9). Subjects were sacrificed 3, 7, and 14 days after coil implantation. Histologic sampl es were studied to assess the presence or absence of nucleated cells within and around coil winds in order to determine whether fibroblasts had been s uccessfully implanted into aneurysms. Data were evaluated using the chi-squ are test for statistical significance. RESULTS: Part 1. Fluorescence-labeled cells were examined in the treatment carotid artery segments and results were recorded at all time intervals. Th e treatment vessel segments showed evidence of progressive cellular prolife ration, leading to complete vessel fibrosis at 2 weeks. Conversely, control vessel segments were filled predominately with unorganized thrombus at eac h time interval. Part 2. A) Numerous labeled fibroblasts remained adherent to the coil despi te prolonged exposure to systemic arterial flow. B) Fibroblasts were seen adjacent to or within the central lumen of coils i n eight (88%) of nine aneurysms treated with cell-bearing coils. Nucleated cells were not present in any of the nine control coil subjects. This repre sented a statistically significant difference (P < .001). CONCLUSION: Fibroblast allografts remain viable and proliferate in the vasc ular space in rabbits. Furthermore, these same fibroblasts, after seeding o nto platinum coils in culture, remain protected within the lumen of the coi ls and are retained within the coil lumen even after prolonged exposure to arterial blood flow. Coils can be used to deliver viable fibroblasts direct ly into experimental aneurysms successfully. These findings indicate that c oil-mediated cell implantation is feasible and may be a potential method of increasing the biological activity of embolic coils.