Abstract 11: Intra-arterial Infusion of Allogeneic Mesenchymal Stem/Stromal Cells is Safe and Enhances Histological Healing in Rabbit Elastase Aneurysms

Abstract

Introduction: Poor healing of coiled intracranial aneurysms results in recanalization and recurrence of the aneurysm in one in five patients. One recent study has shown that intra-arterial infusion of Mesenchymal Stem/Stromal Cells (MSCs) can stop dilation of experimental aneurysms in rabbits. Another study in a mouse model suggests that intravenous delivery of MSCs reduces the risk of aneurysm rupture. MSCs are known for their ability to establish a regenerative microenvironment by inhibiting inflammation, producing trophic factors, and recruiting local progenitors to replace lost cells. In this study, we have conducted a randomized preclinical trial to assess the potential of MSC therapy in improving the healing of coiled aneurysms. Hypothesis: Combined coiling and intra-arterial injection of 5 million allogeneic MSCs will be safe, and will result in superior histological healing of experimental elastase-induced aneurysms in rabbits at 4 weeks post-treatment. Methods: Bone marrow-derived MSCs were isolated from three rabbit donors in a serum-free fashion and were characterized individually. Elastase-induced carotid aneurysms were created in 9 New Zealand White Rabbits. Each subject was randomized to receive one of the following treatments: 1) coiling (treatment group), 2) coiling with an intra-arterial injection of saline solution (vehicle group) and coiling with an intra-arterial injection of 5 million allogeneic MSCs (treatment group). The animals were followed up for 4 weeks, at the end of which a final angiogram and histological analysis was performed. Results: Intra-arterial cell therapy with 5 million allogeneic MSCs did not result in any major adverse events. Histological results showed consistent superior healing in cell therapy group compared with vehicle and control groups. Angiographic results were not significantly different among different study arms. Conclusions: Intra-arterial MSC therapy for intracranial aneurysms is feasible, safe and effective at a proof-of-concept level.