Research Article
Mesenchymal Stem Cells Exhibit Both a Proinflammatory and
Anti-Inflammatory Effect on Saccular Aneurysm Formation in a
Rabbit Model
Michael B. Avery ,
1,2
Brooke L. Belanger ,
2
Amy Bromley ,
3
Arindom Sen ,
4
and Alim P. Mitha
1,5
1
Department of Neurosciences, University of Calgary, Alberta, Canada
2
Neuroscience Graduate Program, University of Calgary, Alberta, Canada
3
Department of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada
4
Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, Alberta, Canada
5
Hotchkiss Brain Institute, University of Calgary, Alberta, Canada
Correspondence should be addressed to Alim P. Mitha; amitha@ucalgary.ca
Received 16 February 2019; Revised 14 May 2019; Accepted 11 June 2019; Published 22 July 2019
Guest Editor: Ming Li
Copyright © 2019 Michael B. Avery et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Several studies have demonstrated a potential interaction between mesenchymal stem cells (MSCs) and saccular aneurysms. In this
study, we sought to determine whether allogenic bone marrow-derived MSCs had the ability to prevent aneurysm formation in a
known rabbit elastase aneurysm model. MSCs were injected intravenously in experimental rabbits at the time of surgical creation
and two weeks postcreation and compared with control rabbits receiving vehicle injection. Angiography was used to compare
aneurysm measurements four weeks postcreation, and aneurysms were harvested for histological properties. Serum was
collected longitudinally to evaluate cytokine alterations. Serum from control animals was also utilized to perform in vitro tests
with MSCs to compare the effect of the serologic environment in animals with and without aneurysms on MSC proliferation
and cytokine production. While aneurysm morphometric comparisons revealed no differences, significant cytokine alterations
were observed in vitro and in vivo, suggesting both anti-inflammatory and proinflammatory processes were occurring in the
presence of MSCs. Histological analyses suggested that tunica intima hyperplasia was inhibited in the presence of MSCs.
1. Introduction
It is estimated that approximately 3% of the general popula-
tion harbors and intracranial saccular aneurysm, a patholog-
ical dilation of the cerebral arteries at bifurcation points that
is prone to rupturing [1]. Aneurysmal rupture occurs in 10 of
every 100,000 people annually and carries with it an esti-
mated mortality rate of 50% and a significant neurological
disability rate among survivors of approximately 30% [2].
Several key changes in the arterial wall occur that are thought
to lead to aneurysm formation, including loss of elastin con-
tent in the internal elastic lamina and reduction of the tunica
media leading to weakening of the wall [3]. Pulsatile blood
pressure forces ensue, leading to outpouching of the thinned
wall. Various inflammatory cascades have been shown to
mediate these processes, with alterations of wall shear
stresses and wall shear stress gradients from hypertension
creating endothelial dysfunction alongside predisposing
patient factors such as smoking [4, 5].
While there are several good treatment options available
for cerebral aneurysms, there is as of yet no viable therapeutic
option to minimize or prevent the initiation or progression of
their pathogenesis. Many prevention strategies have aimed at
disrupting the implicated inflammatory cascades. Unfortu-
nately, they have been fraught with limited success or impos-
sible human application and have largely been focused on
abdominal aortic fusiform aneurysms [6–14]. There is evi-
dence to suggest that saccular and fusiform aneurysms
Hindawi
Stem Cells International
Volume 2019, Article ID 3618217, 15 pages
https://doi.org/10.1155/2019/3618217