title: Intraluminal cell transplantation prevents growth and rupture in a model of rupture-prone saccular aneurysms.
abstract: OBJECTIVE
  Aneurysm occlusion by intraluminal thrombus formation is the desired effect of all endovascular treatments. Intraluminal thrombus may, however, recanalize and be absorbed, unless it is infiltrated by cells that turn it into fibrous tissue (neointima). Because ruptured aneurysm walls are characterized by loss of smooth muscle cells, we assessed the impact of mural cell loss on wall remodeling of thrombosed aneurysms and investigated whether neointima formation could be enhanced by direct transplantation of cells into the thrombus.
  
  
  METHODS
  Sidewall aneurysms were microsurgically created in rats (n=81). Certain aneurysms were decellularized. Thrombosis was induced using direct injection of a fibrin polymer into the aneurysm. CM-Dil-labeled smooth muscle cells were injected into 25 of 46 fibrin embolized aneurysms. Recanalization and aneurysm growth were monitored with magnetic resonance angiography. Endoscopy, optical projection tomography, histology, and immunohistochemistry were used to study the fate of transplanted cells, thrombus organization, and neointima formation.
  
  
  RESULTS
  Decellularized embolized aneurysms demonstrated higher angiographic recurrence compared with decellularized embolized aneurysms with transplanted cells (P=0.037). Local cell replacement at the time of thrombosis resulted in better histological neointima formation than both nondecellularized embolized aneurysms (P<0.001) and decellularized embolized aneurysms (P=0.002). Aneurysm growth and rupture were observed exclusively in decellularized embolized aneurysms.
  
  
  CONCLUSIONS
  Lack of smooth muscle cells in the aneurysm wall promotes wall degradation, aneurysm growth and rupture, even if the aneurysm is occluded by luminal thrombus. Transplantation of smooth muscle cells into the luminal thrombus can reduce this degenerative remodeling.
authors.affiliation: From the Department of Neurosurgery, Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland (S.M., J.F., J.M., P.H., J.H., M.N.); Wihuri Research Institute, Translational Cancer Biology Program, Biomedicum Helsinki (A.A.) and Department of Neurology, Institute of Biomedicine, Experimental MRI Laboratory (U.A.-R.), University of Helsinki, Helsinki, Finland; and Institute of Pathology Laenggasse, Bern, Switzerland (M.v.G.). serge.marbacher@ksa.ch.
authors.forename: Serge
authors.initials: S
authors.lastname: Marbacher
authors.affiliation: From the Department of Neurosurgery, Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland (S.M., J.F., J.M., P.H., J.H., M.N.); Wihuri Research Institute, Translational Cancer Biology Program, Biomedicum Helsinki (A.A.) and Department of Neurology, Institute of Biomedicine, Experimental MRI Laboratory (U.A.-R.), University of Helsinki, Helsinki, Finland; and Institute of Pathology Laenggasse, Bern, Switzerland (M.v.G.).
authors.forename: Juhana
authors.initials: J
authors.lastname: Frösén
authors.affiliation: From the Department of Neurosurgery, Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland (S.M., J.F., J.M., P.H., J.H., M.N.); Wihuri Research Institute, Translational Cancer Biology Program, Biomedicum Helsinki (A.A.) and Department of Neurology, Institute of Biomedicine, Experimental MRI Laboratory (U.A.-R.), University of Helsinki, Helsinki, Finland; and Institute of Pathology Laenggasse, Bern, Switzerland (M.v.G.).
authors.forename: Johan
authors.initials: J
authors.lastname: Marjamaa
authors.affiliation: From the Department of Neurosurgery, Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland (S.M., J.F., J.M., P.H., J.H., M.N.); Wihuri Research Institute, Translational Cancer Biology Program, Biomedicum Helsinki (A.A.) and Department of Neurology, Institute of Biomedicine, Experimental MRI Laboratory (U.A.-R.), University of Helsinki, Helsinki, Finland; and Institute of Pathology Laenggasse, Bern, Switzerland (M.v.G.).
authors.forename: Andrey
authors.initials: A
authors.lastname: Anisimov
authors.affiliation: From the Department of Neurosurgery, Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland (S.M., J.F., J.M., P.H., J.H., M.N.); Wihuri Research Institute, Translational Cancer Biology Program, Biomedicum Helsinki (A.A.) and Department of Neurology, Institute of Biomedicine, Experimental MRI Laboratory (U.A.-R.), University of Helsinki, Helsinki, Finland; and Institute of Pathology Laenggasse, Bern, Switzerland (M.v.G.).
authors.forename: Petri
authors.initials: P
authors.lastname: Honkanen
authors.affiliation: From the Department of Neurosurgery, Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland (S.M., J.F., J.M., P.H., J.H., M.N.); Wihuri Research Institute, Translational Cancer Biology Program, Biomedicum Helsinki (A.A.) and Department of Neurology, Institute of Biomedicine, Experimental MRI Laboratory (U.A.-R.), University of Helsinki, Helsinki, Finland; and Institute of Pathology Laenggasse, Bern, Switzerland (M.v.G.).
authors.forename: Michael
authors.initials: M
authors.lastname: von Gunten
authors.affiliation: From the Department of Neurosurgery, Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland (S.M., J.F., J.M., P.H., J.H., M.N.); Wihuri Research Institute, Translational Cancer Biology Program, Biomedicum Helsinki (A.A.) and Department of Neurology, Institute of Biomedicine, Experimental MRI Laboratory (U.A.-R.), University of Helsinki, Helsinki, Finland; and Institute of Pathology Laenggasse, Bern, Switzerland (M.v.G.).
authors.forename: Usama
authors.initials: U
authors.lastname: Abo-Ramadan
authors.affiliation: From the Department of Neurosurgery, Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland (S.M., J.F., J.M., P.H., J.H., M.N.); Wihuri Research Institute, Translational Cancer Biology Program, Biomedicum Helsinki (A.A.) and Department of Neurology, Institute of Biomedicine, Experimental MRI Laboratory (U.A.-R.), University of Helsinki, Helsinki, Finland; and Institute of Pathology Laenggasse, Bern, Switzerland (M.v.G.).
authors.forename: Juha
authors.initials: J
authors.lastname: Hernesniemi
authors.affiliation: From the Department of Neurosurgery, Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland (S.M., J.F., J.M., P.H., J.H., M.N.); Wihuri Research Institute, Translational Cancer Biology Program, Biomedicum Helsinki (A.A.) and Department of Neurology, Institute of Biomedicine, Experimental MRI Laboratory (U.A.-R.), University of Helsinki, Helsinki, Finland; and Institute of Pathology Laenggasse, Bern, Switzerland (M.v.G.).
authors.forename: Mika
authors.initials: M
authors.lastname: Niemelä
mesh_terms: D000783:Aneurysm / Q000473:pathology* / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic / Q000379:methods; D005455:Fluorescent Antibody Technique; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000637:transplantation*; D051381:Rats; D017208:Rats, Wistar
keywords: cell transplantation; degeneration; inflammation; intracranial aneurysm; myofibroblasts; smooth muscle cells; thrombosis