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Original research
Autologous adipose-derived mesenchymal stem cells improve healing of coiled experimental saccular aneurysms: an angiographic and histopathological study
  1. Aymeric Rouchaud1,2,
  2. Waleed Brinjikji3,
  3. Daying Dai1,
  4. Yong-Hong Ding1,
  5. Tina Gunderson4,
  6. Dana Schroeder1,
  7. Laurent Spelle2,
  8. David F Kallmes1,
  9. Ramanathan Kadirvel1
  1. 1Applied Neuroradiology Laboratory, Mayo Clinic, Rochester, Minnesota, USA
  2. 2Department of Interventional Neuroradiology, NEURI Center, Le Kremlin-Bicetre, France
  3. 3Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
  4. 4Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, USA
  1. Correspondence to Dr Aymeric Rouchaud, Applied Neuroradiology Laboratory, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA; aymeric.rouchaud{at}gmail.com

Abstract

Purpose 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.

Materials and 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. χ2 and 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 μm2 vs 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.

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Footnotes

  • Contributors AR, DFK, and RK participated in the conception and design of the study. AR, DD and WB participated in drafting the article. AR, WB, LS, DFK, and RK participated in revising it critically for important intellectual content. AR, WB, DD, YHD, TG, LS, DFK, and RK made substantial contributions to conception and design, acquisition of the data, and analysis and interpretation of the data. All authors provided final approval of the version to be published.

  • Funding This work was supported by research grant NS0767491 from the National Institute of Health and Medtronics. This work was partially funded by the SNIS Foundation Fellow Research Grant. AR was supported by research grants from the French Society of Radiology and Therese Planiol Foundation.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The data discussed in this article are taken from our institution. Unpublished data may be available on request to the corresponding author.

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