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  • Mesenchymal Stem Cells Localize to Developing Saccular Aneurysms

    Final Number:
    152

    Authors:
    Michael Avery MD, BSc, MSc; Winston Ying MD; Arindom Sen PhD; Alim P. Mitha MD SM

    Study Design:
    Laboratory Investigation

    Subject Category:
    Basic Science

    Meeting: AANS/CNS Cerebrovascular Section 2018 Annual Meeting

    Introduction: Mesenchymal stem cells (MSCs) administered into saccular aneurysms have been shown to promote aneurysm healing. (1-3) Our lab has found that MSCs administered intravenously (IV) during the formation of saccular aneurysms inhibit tunica intima hyperplasia. We sought to determine whether MSCs localize to the developing aneurysm or secrete factors from the pulmonary capillary bed after being entrapped by injecting MSCs labelled with technetium-99m (Tc)

    Methods: Eight rabbits were randomly assigned to three control groups (Tc Control (1), MSC Control (1), Sham Control (2)) and two experimental groups (Day 1 Aneurysm (2), Day 15 Aneurysm (2)). Right common carotid artery (CCA) saccular aneurysms were surgically created using elastase in the experimental group and a sham procedure was performed in the Sham Control rabbits. All rabbits received Tc-MSCs IV immediately prior to planar scintigraphy. Image acquisition occurred at 3 hours post-injection, with one rabbit in each surgical group undergoing acquisition at 21 hours. The Tc Control rabbit received Tc alone. Signal in the right CCA region was measured in all rabbits. After image acquisition, the right CCA and 1cc of arterial blood was harvested from all rabbits and placed in a gamma counter for highly sensitive radioactivity quantification.

    Results: ystemic distribution of Tc-MSCs differed from Tc, indicating stable Tc tag. All Tc-MSC – injected rabbits demonstrated similar systemic distributions with early and persistent lung signal. While no signal was observed in the CCA/aneurysm, harvested tissues demonstrated increased activity in the Day 1 and 15 aneurysms at 3 and 21 hours compared to Sham Control rabbits.

    Conclusions: MSCs injected IV become entrapped in the rabbit lung, with a portion traversing the pulmonary capillary bed and localizing to the developing aneurysm both 1 and 15 days after creation. It is postulated that the inflammatory milieu of aneurysm pathogenesis acts as a localizing signal for MSCs.

    Patient Care: Our research demonstrates a potential mechanism by which mesenchymal stem cells may improve the healing of saccular aneurysms. These findings may be used to further tailor therapeutic intervention experiments with mesenchymal stem cells and contribute to the design of clinical trials.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the impact that mesenchymal stem cells have on developing aneurysms 2) Describe the effects of mesenchymal stem cells have on aneurysm healing as an adjunctive treatment in experimental models 3) Describe the systemic distribution of mesenchymal stem cells upon IV injection and their localization to developing aneurysms

    References: 1. Adibi A, Eesa M, Wong JH, Sen A, Mitha AP. Combined endovascular coiling and intra-aneurysmal allogeneic mesenchymal stromal cell therapy for intracranial aneurysms in a rabbit model: a proof-of-concept study. J Neurointerv Surg. 2017. 9(7):707-12. 2. Rouchaud A, Brinjikji W, Dai D, Ding YH, Gunderson T, Schroeder D et al. Autologous adipose-derived mesenchymal stem cells improve healing of coiled experimental saccular aneurysms: an angiographic and histopathological study. J Neurointerv Surg. 2017. doi: 10.1136/neurintsurg-2016-012867. 3. Rouchaud A, Journe C, Louedec L, Ollivier V, Derkaoui M, Michel JB et al. Autologous mesenchymal stem cell endografting in experimental cerebrovascular aneurysms. Neuroradiology. 2013. 55(6):741-9.

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