Intraluminal cell transplantation prevents growth and rupture in a model of rupture-prone saccular aneurysms

Abstract

Background and purpose: 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.

Keywords: cell transplantation; degeneration; inflammation; intracranial aneurysm; myofibroblasts; smooth muscle cells; thrombosis.