Contribution of mural and bone marrow-derived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model.

Abstract:

OBJECTIVE:Endovascular occlusive therapy of human saccular cerebral artery aneurysms may fail because of thrombus recanalization and incomplete neointima formation. Bone marrow-derived progenitor cells may contribute to these processes, but their role in human saccular cerebral artery aneurysms and experimental aneurysm models remains unclear. METHODS:Experimental saccular aneurysms were constructed from syngeneic thoracic aortas transplanted end-to-side to the abdominal aorta of Wistar rats (n = 14), C57/B6 mice (n = 13), ApoE mice (n = 7), reporter gene expressing ROSA mice (n = 7), and mice with labeled bone marrow (ROSA [n = 12] or green fluorescent protein [n = 3]). Magnetic resonance imaging or angiography was used to monitor patency of the experimental aneurysms. Histology and immunohistochemistry were used to study thrombus organization and neointima formation and X-gal staining and confocal microscopy to study the origin of neointimal cells. RESULTS:Experimental aneurysms developed luminal pads of neointimal hyperplasia or organizing thrombosis that became thicker and occluded partly the lumen at later time points during the first week. Reporter gene mice (ROSA) revealed that 42 to 81% (median, 58%) of neointimal hyperplasia/organizing thrombosis was derived from the experimental aneurysm wall. Bone marrow-derived neointimal cells were found in only 5 of 15 mice (range, 11-73 per section; a median of 22 cells among a total of 2000-6000 wall cells). CONCLUSION:Thrombus organizing or neointimal cells were mostly derived from the experimental aneurysm wall, with only a minor contribution from the bone marrow. In human saccular cerebral artery aneurysms, the contribution of bone marrow-derived neointimal cells might be more important and should be compared with that found in other experimental models used to develop endovascular therapies.

journal_name

Neurosurgery

journal_title

Neurosurgery

authors

Frösen J,Marjamaa J,Myllärniemi M,Abo-Ramadan U,Tulamo R,Niemelä M,Hernesniemi J,Jääskeläinen J

doi

10.1227/01.NEU.0000210260.55124.A4

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

936-44; discussion 936-44

issue

5

eissn

0148-396X

issn

1524-4040

pii

00006123-200605000-00018

journal_volume

58

pub_type

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