• Atsushi Kuwabara, Jia Liu, Yoshinobu Kamio, Airan Liu, Michael T Lawton, Jae-Woo Lee, and Tomoki Hashimoto.
• Departments of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California.
• Neurosurgery. 2017 Dec 1; 81 (6): 1021-1028.

BackgroundMesenchymal stem cells (MSCs) are multipotent stem or stromal cells found in multiple tissues. Intravenous MSC injections have been used to treat various diseases with an inflammatory component in animals and humans. Inflammation is emerging as a key component of pathophysiology of intracranial aneurysms. Modulation of inflammation by MSCs may affect sustained inflammatory processes that lead to aneurysmal rupture.ObjectiveTo assess the effect of MSCs on the development of aneurysm rupture using a mouse model.MethodsIntracranial aneurysms were induced with a combination of a single elastase injection into the cerebrospinal fluid and deoxycorticosterone acetate salt-induced hypertension in mice. We administered allogeneic bone marrow-derived MSCs or vehicle, 6 and 9 d after aneurysm induction.ResultsMSC administration significantly reduced rupture rate (vehicle control vs MSCs, 90% vs 36%; P < .05). In cell culture experiments with an MSC and mast cell coculture, MSCs stabilized mast cells through cyclooxygenase-2 (COX-2)-dependent production of prostaglandin E2, thereby reducing the release of proinflammatory cytokines from mast cells. Pretreatment of MSCs with COX-2 inhibitor, NS-398, abolished the protective effect of MSCs against the development of aneurysm rupture.ConclusionIntravenous administration of MSCs after aneurysm formation prevented aneurysmal rupture in mice. The protective effect of MSCs against the development of aneurysm rupture appears to be mediated in part by the stabilization of mast cells by MSCs.Copyright © 2017 by the Congress of Neurological Surgeons

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