title: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurosurgery Research Group, Biomedicum Helsinki, and Transplantation Laboratory, University of Helsinki, Helsinki, Finland. frosen@kuh.fi
authors.forename: Juhana
authors.initials: J
authors.lastname: Frösen
authors.forename: Johan
authors.initials: J
authors.lastname: Marjamaa
authors.forename: Marjukka
authors.initials: M
authors.lastname: Myllärniemi
authors.forename: Usama
authors.initials: U
authors.lastname: Abo-Ramadan
authors.forename: Riikka
authors.initials: R
authors.lastname: Tulamo
authors.forename: Mika
authors.initials: M
authors.lastname: Niemelä
authors.forename: Juha
authors.initials: J
authors.lastname: Hernesniemi
authors.forename: Juha
authors.initials: J
authors.lastname: Jääskeläinen
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000379:methods; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D002532:Intracranial Aneurysm / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008866:Microsurgery / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000209:etiology / Q000473:pathology*; D017539:Tunica Intima / Q000473:pathology*