Endothelial progenitor cells contribute to neointima formation in rabbit elastase-induced aneurysm after flow diverter treatment

Aims: Endothelial progenitor cells (EPCs) are involved in vascular repair and homeostasis after vascular injuries. In this study, we aimed to explore whether bone marrow (BM)-derived EPCs contribute to neointima formation and reendothelialization in rabbit elastase-induced aneurysm after flow diverter treatment.

Methods: Elastase-induced aneurysms were created in New Zealand male rabbits. Three weeks after model creation, flow diverter was implanted to cover the induced aneurysm neck. Autologous EPCs were isolated from bone marrow, expanded ex vivo, double labeled with Hoechst 33,342 and CFSE(carboxyfluorescein diacetate succinimidyl ester), and transplanted transvenously into the rabbits. The rabbits were assigned into three groups. The first group received autologous transfusion of double-labeled EPCs from the first day after stent implantation, and the second group received transfusion from the fifteenth day. The autologous transfusion was given at a 3-day interval and continued for 2 weeks. Fluorescence-labeled cells were tracked under fluorescence microscope at the aneurysm neck and parent artery in the two groups. The third group was established as control group without EPCs transplantation. Scanning electron microscope was used to investigate the reendothelialization rate between the former two groups and the control group.

Results: In the first group, double-positive EPCs were found in 3/5 rabbits and mainly located in the subendothelial space and around the stent struts. In the second group, double-positive EPCs were found in 2/5 rabbits and mainly located on the surface of neointima. More endothelial-like cells were observed on the neointima of aneurysm neck and stented parent artery in the groups with EPCs transplantation than control group without EPCs transplantation, but the difference on the number of these cells did not reach statistical significance.

Conclusions: BM-derived EPCs participate in neointima formation and reendothelialization in elastase-induced aneurysm after flow diverter treatment. The EPCs may differentiate into different cell types according to the stages of neointima formation in vivo.