Endovascular Treatment of Experimental Aneurysms by Use of Biologically Modified Embolic Devices: Coil-mediated Intraaneurysmal Delivery of Fibroblast Tissue Allografts
William F. Marx,a,
Harry J. Clofta,
Gregory A. Helma,
John G. Shorta,
Huy M. Doa,
Mary E. Jensena and
David F. Kallmesa
a From the Departments of Radiology (W.F.M., J.G.S., M.E.J., D.F.K.) and Neurosurgery (G.H.), University of Virginia Health Sciences Center, Charlottesville, VA; the Department of Radiology (H.J.C.), Emory University, Atlanta, GA; and the Department of Radiology (H.M.D.), Stanford University, Palo Alto, CA.
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FIG 1. Electron microscopy image of GDC coils co-cultured with fibroblasts. Note fibroblasts growing on surface (A) and within the central lumen (B) of the coils
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FIG 2. A, Experimental aneurysm accessed with microcatheter.
B, Coils deployed under roadmap fluoroscopy.
C, Control angiogram shows complete occlusion of the aneurysm.
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FIG 3. A, 14-day H&E-stained control aneurysm filled with unorganized thrombus.
B, 100x magnification shows coil wind surrounded only by RBCs.
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FIG 4. A, 40x H&E-stained 3-day sample showing coil bridging aneurysm neck.
B, 100x H&E-stained slide demonstrating nucleated cells within coil interstices (arrows) adjacent to endothelialized aneurysm neck.
C, 400x magnification shows fibroblasts (arrows) present within central lumen of coil.
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FIG 5. A, 100x H&E-stained 7-day sample. The arrow marks tissue that was present within the central lumen of the implanted coil. The basophilic, nucleated cells in the central region (arrow) are transplanted fibroblasts.
B, 400x magnification demonstrates fibroblasts (arrows) present within central lumen of coil.
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FIG 6. A, 40x H&E-stained view of 14-day speciment embolized with fibroblast-bearing GDC coil. The coil bridged the aneurysm neck, which developed neoendothelial lining.
B, 100x view of same specimen illustrates fibroblasts (arrow) present within the coil wind interstices and extending into the adjacent thrombus and aneurysm neck.
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FIG 7. Treatment vessels containing implanted fibroblasts (A–C) and control vessels (D–F) at 3-day (A and D), 7-day (B and E), and 14-day (C and F) intervals. Treatment vessels show progressive intraluminal cellular proliferation and fibrosis (arrows). Control vessels are filled with unorganized thrombus with scant cellular infiltration. Star indicates vessel wall
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FIG 8. H&E (A) and fluorescent micrograph (B) of artery segment implanted 2 weeks previously with fluorescently labeled cells. The lumen of the arterial segment is nearly completely occluded, with a dense cellular infiltrate. The fluorescent images confirm the presence of labeled cells that are most intensely labeled in the central lumen of the vessel. Weak fluorescent labeling of the cells peripherally is likely secondary to the dilution effect on the membrane dye owing to cell division
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FIG 9. Estimated percent fibrosis of the treatment and control vessels at each time interval. There was no organized fibrosis in the control vessels at any time point. The treatment vessels had fibroblast proliferation at 3 days, progressing to complete fibrosis of the vessel lumen at 14 days
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FIG 10. Segments of GDC coils co-cultured with fluorescence-labeled fibroblasts.
A, Fluorescent cells in culture adherent to the surface of the coil and extending into interstices of the coil lumen.
B, Immediately after withdrawal of coil into housing, the cells on the surface are stripped. Cells remain within coil lumen. Coils exposed to systemic arterial flow for 5 minutes (C), 10 minutes (D), 20 minutes (E), and 40 minutes (F). Numerous cells remain at all time intervals. The density of cells is diminished at the 20- and 40-minute time points relative to earlier samples.
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FIG 11. Histologic grade immediately adjacent to the implanted coils on the basis of the presence and amount of nucleated fibroblasts. Fibroblasts were seen adjacent to or within the central lumen of coils in eight (88%) of nine anuerysms treated with cell-bearing GDCs. Nucleated cells were present in none of the nine control coil subjects
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