In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling

J Neurointerv Surg. 2021 Mar;13(3):267-271. doi: 10.1136/neurintsurg-2020-016589. Epub 2020 Oct 5.


Objective: To investigate in situ decellularization of a large animal model of saccular aneurysm as a strategy for achieving aneurysmal growth and lasting inflammation.

Methods: 18 New Zealand White rabbits were randomized 2:1 to receive endoluminal sodium dodecyl sulfate infusion (SDS, 1% solution, 45 min) following elastase or elastase-only treatment (control). All aneurysms were measured by digital subtraction angiography every 2 weeks. Every 2 weeks, three of the rabbits (two elastase + SDS, one control) underwent MRI, followed by contrast injection with myeloperoxidase (MPO)-sensing contrast agent. MRI was repeated 3 hours after contrast injection and the enhancement ratio (ER) was calculated. Following MRI, aneurysms were explanted and subjected to immunohistopathology.

Results: During follow-up MRI, the average ER for SDS-treated animals was 1.63±0.20, compared with 1.01±0.06 for controls (p<0.001). The width of SDS-treated aneurysms increased significantly in comparison with the elastase aneurysms (47% vs 20%, p<0.001). Image analysis of thin sections showed infiltration of MPO-positive cells in decellularized aneurysms and surroundings through the 12-week observation period while control tissue had 5-6 times fewer cells present 2 weeks after aneurysm creation. Immunohistochemistry demonstrated the presence of MPO-positive cells surrounding decellularized lesions at early time points. MPO-positive cells were found in the adventitia and in the thrombi adherent to the aneurysm wall at later time points.

Conclusions: In situ decellularization of a large animal model of saccular aneurysms reproduces features of unstable aneurysms, such as chronic inflammation (up to 12 weeks) and active aneurysm wall remodeling, leading to continued growth over 8 weeks.

Keywords: MRI; aneurysm; inflammation.

MeSH terms

  • Aneurysm / diagnostic imaging*
  • Aneurysm / pathology
  • Angiography, Digital Subtraction / methods
  • Animals
  • Disease Models, Animal*
  • Endothelium, Vascular / diagnostic imaging*
  • Endothelium, Vascular / pathology
  • Female
  • Image Processing, Computer-Assisted / methods
  • Inflammation / diagnostic imaging
  • Inflammation / pathology
  • Magnetic Resonance Imaging / methods
  • Male
  • Rabbits
  • Random Allocation
  • Vascular Remodeling / physiology*