title: Endovascular treatment of experimental aneurysms by use of biologically modified embolic devices: coil-mediated intraaneurysmal delivery of fibroblast tissue allografts.
abstract: OBJECTIVE
  Our long-term goal is to improve intraaneurysmal fibrosis after aneurysm embolization, by implanting exogenous fibroblasts, using platinum coils. For the current project, we tested two hypotheses: 1) that exogenous, fluorescence-labeled rabbit fibroblast allografts remained viable and proliferated within rabbit carotid arteries, and 2) that these fibroblast allografts could be reliably implanted into experimental aneurysms by use of platinum coils.
  
  
  METHODS
  Part 1. New Zealand White rabbit synovial fibroblasts obtained from a commercial vender were labeled with a fluorescent membrane marker. The common carotid arteries of New Zealand White rabbits were surgically exposed, ligated proximally and distally, and entered with 22-g angiocatheters. Through the angiocatheter we injected either phosphate-buffered saline-containing 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 staining. 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 coils, which were then exposed to systemic arterial flow in the rabbit thoracic aorta for various lengths of time up to 40 minutes. The coil segments were 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 coils (n = 9) and platinum coils bearing rabbit synovial fibroblasts that were grown onto the coils in culture prior to implantation (n = 9). Subjects were sacrificed 3, 7, and 14 days after coil implantation. Histologic samples were studied to assess the presence or absence of nucleated cells within and around coil winds in order to determine whether fibroblasts had been successfully implanted into aneurysms. Data were evaluated using the chi-square 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. The treatment vessel segments showed evidence of progressive cellular proliferation, leading to complete vessel fibrosis at 2 weeks. Conversely, control vessel segments were filled predominately with unorganized thrombus at each time interval. Part 2. A) Numerous labeled fibroblasts remained adherent to the coil despite prolonged exposure to systemic arterial flow. B) Fibroblasts were seen adjacent to or within the central lumen of coils in eight (88%) of nine aneurysms treated with cell-bearing coils. Nucleated cells were not present in any of the nine control coil subjects. This represented a statistically significant difference (P < .001).
  
  
  CONCLUSIONS
  Fibroblast allografts remain viable and proliferate in the vascular space in rabbits. Furthermore, these same fibroblasts, after seeding onto platinum coils in culture, remain protected within the lumen of the coils and are retained within the coil lumen even after prolonged exposure to arterial blood flow. Coils can be used to deliver viable fibroblasts directly into experimental aneurysms successfully. These findings indicate that coil-mediated cell implantation is feasible and may be a potential method of increasing the biological activity of embolic coils.
authors.affiliation: Department of Radiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Marx
authors.forename: H J
authors.initials: HJ
authors.lastname: Cloft
authors.forename: G A
authors.initials: GA
authors.lastname: Helm
authors.forename: J G
authors.initials: JG
authors.lastname: Short
authors.forename: H M
authors.initials: HM
authors.lastname: Do
authors.forename: M E
authors.initials: ME
authors.lastname: Jensen
authors.forename: D E
authors.initials: DE
authors.lastname: Kallmes
mesh_terms: D000818:Animals; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D004621:Embolization, Therapeutic / Q000295:instrumentation* / Q000379:methods*; D004867:Equipment Design; D005240:Feasibility Studies; D005347:Fibroblasts / Q000502:physiology / Q000637:transplantation*; D005471:Fluoroscopy; D002532:Intracranial Aneurysm / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D010984:Platinum; D011817:Rabbits; D013997:Time Factors
chemical_list: D020099:Coated Materials, Biocompatible; D010984:Platinum