Introduction: Aneurysmal subarachnoid hemorrhage is the most fatal type of stroke with high morbidity and mortality. Better understanding of cerebral aneurysms is required to improve the management of the disease, and further research on aneurysms can be achieved by using canines as research models. It also has been shown that mesenchymal stem cells (MSC) accumulate in damaged tissue and secrete anti-inflammatory agents which have been reported to promote the synthesis of elastin. This offers another potential treatment modality for cerebral aneurysms.

Methods: Four canines were involved in the study. They were positioned in supine position with neck extension. A linear skin incision was made in the neck, 5cm above sternum. Dissection was performed and the right common carotid artery was identified. The carotid artery was then followed proximally to its branch point from the brachiocephalic artery. The distal point of the right common carotid artery was then tied off to create aneurysm. Bone marrow from pelvis was also aspirated during the surgery. MSCs were later derived from the bone marrow sample. After the surgery, MRIs were obtained using ferumoxytol to monitor the progression of the aneurysms. In post-operative week 3, these aneurysms were treated with MSCs using the endovascular technique. In post-operative week 6, they were sacrificed to harvest the aneurysms.

Results: Aneurysm was created off of the brachiocephalic artery. Subsequent MRIs revealed a persistent opening of the aneurysm off of the brachiocephalic artery (Figure 1.0). The aneurysm was seen during its harvest (Figure 2.0). No subjects suffered any medical harm after the surgery or injection of MSCs through micro-catheter in endovascular technique.

Conclusions: Successful development of the stable canine aneurysm model in the neck was achieved. Its size and shape can be easily assessed and monitored using MRI. We also concluded that injection of MSCs through micro-catheter is safe. Therefore, future studies will focus on intra-arterial delivery of the cells to treat aneurysms in this model.

Patient Care: Better understanding of cerebrovascular aneurysm will eventually lead us to better patient care

Learning Objectives: By the conclusion of this session, participants should be able to: 1) know that stable and successful canine aneurysm model is created 2) further study on aneurysm can be achieved using the canine aneurysm model 3) mesenchymal stem cells can be considered for treatment of aneurysm

References: Hop JW, Rinkel GJ, Algra A, van Gijn J. Case-fatality rates and functional outcome after subarachnoid hemorrhage: A systematic review. Stroke. 1997;28:660-664 Yuan L, Sakamoto N, Song G, Sato M. Low-level shear stress induces human mesenchymal stem cell migration through the sdf-1/cxcr4 axis via mapk signaling pathways. Stem Cells Dev. 2013;22:2384-2393 Xinaris C, Morigi M, Benedetti V, Imberti B, Fabricio AS, Squarcina E, Benigni A, Gagliardini E, Remuzzi G. A novel strategy to enhance mesenchymal stem cell migration capacity and promote tissue repair in an injury specific fashion. Cell Transplant. 2013;22:423-436 Liu X, Liao X, Luo E, Chen W, Bao C, Xu HH. Mesenchymal stem cells systemically injected into femoral marrow of dogs home to mandibular defects to enhance new bone formation. Tissue Eng Part A. 2014;20:883-892 Knaan-Shanzer S. Concise review: The immune status of mesenchymal stem cells and its relevance for therapeutic application. Stem Cells. 2014;32:603-608 Ogle BM, Mooradian DL. The role of vascular smooth muscle cell integrins in the compaction and mechanical strengthening of a tissue-engineered blood vessel. Tissue Eng. 1999;5:387-402 Santiago JA, Pogemiller R, Ogle BM. Heterogeneous differentiation of human mesenchymal stem cells in response to extended culture in extracellular matrices. Tissue Eng Part A. 2009;15:3911-3922 Nan Z, Grande A, Sanberg CD, Sanberg PR, Low WC. Infusion of human umbilical cord blood ameliorates neurologic deficits in rats with hemorrhagic brain injury. Ann N Y Acad Sci. 2005;1049:84-96 Philippe B, Luc S, Valerie PB, Jerome R, Alessandra BR, Louis C. Culture and use of mesenchymal stromal cells in phase i and ii clinical trials. Stem Cells Int. 2010;2010:503593