title: Autologous adipose-derived mesenchymal stem cells improve healing of coiled experimental saccular aneurysms: an angiographic and histopathological study.
abstract: OBJECTIVE
  Long-term occlusion of coiled aneurysms frequently fails, probably because of poor intrasaccular healing and inadequate endothelialization across the aneurysm neck. The purpose of this study was to determine if attachment of autologous mesenchymal stem cells (MSCs) to platinum coils would improve the healing response in an elastase-induced aneurysm model in rabbits.
  
  
  METHODS
  With approval from the institutional animal care and use committee, aneurysms were created in rabbits and embolized with control platinum coils (Axium; Medtronic) (n=6) or coils seeded ex vivo with autologous adipose-tissue MSCs (n=7). Aneurysmal occlusion after embolization was evaluated at 1 month with angiography. Histological samples were analyzed by gross imaging and graded on the basis of neck and dome healing on H&E staining. Fibrosis was evaluated using a ratio of the total area presenting collagen. Endothelialization of the neck was quantitatively analyzed using CD31 immunohistochemistry. χ2and Student's t-test were used to compare groups.
  
  
  RESULTS
  Healing score (11.5 vs 8.0, p=0.019), fibrosis ratio (10.3 vs 0.13, p=0.006) and endothelialization (902 262 μm2vs 31 810 μm2, p=0.041) were significantly greater in the MSC group. The MSC group showed marked cellular proliferation and thrombus organization, with a continuous membrane bridging the neck of the aneurysm. Angiographic stable or progressive occlusion rate was significantly lower in the MSC group (0.00, 95% CI 0.00 to 0.41) compared with controls (0.67, 95% CI 0.22 to 0.96) (p=0.02).
  
  
  CONCLUSIONS
  Autologous MSCs attached to platinum coils significantly improve histological healing, as they result in improved neck endothelialization and collagen matrix formation within the aneurysm sac.
authors.affiliation: Applied Neuroradiology Laboratory, Mayo Clinic, Rochester, Minnesota, USA.|Department of Interventional Neuroradiology, NEURI Center, Le Kremlin-Bicetre, France.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Rouchaud
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Waleed
authors.initials: W
authors.lastname: Brinjikji
authors.affiliation: Applied Neuroradiology Laboratory, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Daying
authors.initials: D
authors.lastname: Dai
authors.affiliation: Applied Neuroradiology Laboratory, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Ding
authors.affiliation: Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Gunderson
authors.affiliation: Applied Neuroradiology Laboratory, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Schroeder
authors.affiliation: Department of Interventional Neuroradiology, NEURI Center, Le Kremlin-Bicetre, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Spelle
authors.affiliation: Applied Neuroradiology Laboratory, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Kallmes
authors.affiliation: Applied Neuroradiology Laboratory, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Kadirvel
mesh_terms: D000273:Adipose Tissue / Q000637:transplantation*; D000818:Animals; D002478:Cells, Cultured; D002533:Cerebral Angiography / Q000379:methods*; D004621:Embolization, Therapeutic / Q000379:methods; D057510:Endovascular Procedures / Q000379:methods*; D002532:Intracranial Aneurysm / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011817:Rabbits; D014182:Transplantation, Autologous
keywords: Aneurysm; Bioactive; Technique