Perivascular scaffolds loaded with adipose tissue‐derived stromal cells attenuate development and progression of abdominal aortic aneurysm in rats

Abstract

Abdominal aortic aneurysm (AAA) is the pathological dilation and weakening of the abdominal aorta wall. Inflammation, degradation of the extracellular matrix (ECM) and loss of smooth muscle cells and skewing of their function are pivotal in AAA pathology. We developed a recombinant collagen-based patch (RCP) to provide structural integrity and deliver Adipose tissue-Derived Stromal Cells (ASC) for repair. Patches supported adhesion and function as well as proliferation of ASC. ASC-loaded RCPs or bare patches, applied around the aorta after AAA induction in rats, both maintained structural integrity of the aortic wall at time of explant (2w). However, wall thinning, accompanied by loss of elastin fibers and loss of medial SMC, was only attenuated in ASC-loaded RCP-treated AAA rats. Interestingly, this coincided with migration of ASC into the media and a reduced influx of macrophages. We hypothesize that the medially-migrated ASC dampened or skewed the adverse innate immunity and thus suppressed SMC apoptosis, phenotypic skewing and elastin degradation. We conclude that the periadventitial delivery of ASC with RCP suppresses development and progression of AAA, which is has an expected future clinical benefit in combination with an appropriate early screening program of patients at risk for aneurysms. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2494-2506, 2018.

Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague-Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation

“…In this study, a single dose of 1 × 10 6 UC-MSCs were injected intravenously on the 1st postoperative day, which gave rise to considerations about optimal injecting cell amount, along with the frequency and timing of injection. Compared to studies with local implantation of MSCs [ 15 , 20 ], intravenous injection of MSCs represents the minimum invasive systematic route for cellular therapy, and has been previously shown to be effective in different AAA models [ 16 , 18 , 34 ]. In addition, a randomized controlled trail investigating MSCs in small human AAA also applied intravenous administration [ 58 ], which further arise the clinical convenience and feasibility of intravenous administration.…”

“…Recently, preclinical studies have found mesenchymal stem cell (MSC)-based cellular therapy is beneficial to AAA initiation and progression [14][15][16][17][18][19][20][21]. Parvizi et al [20,21] demonstrated that perivascular scaffolds loaded with adipose-derived MSCs could attenuate AAA development, prevent loss of VSMCs, and decrease macrophage infiltration in rats. Sharma et al [19] found that intravenous injection of umbilical cord mesenchymal stem cells (UC-MSCs) attenuates proinflammatory cytokine IL-17 production and protects against AAA formation.…”

Disturbed flow's impact on cellular changes indicative of vascular aneurysm initiation, expansion, and rupture: A pathological and methodological review

“…Although the injection of MSCs into the aneurysmal wall holds promise for improving aneurysmal tissue, such direct injection methods come with an increased risk of damaging an already weakened vascular wall. As an alternative method, developing cells loaded onto perivascular scaffolds and applied periadventitialy suppressed development and progression of AAA in rats without the need for direct injection (Parvizi et al, 2018). Although regenerative medicine‐based approaches can potentially treat aneurysms, further studies are required to better understand how MSCs influence aneurysm pathology.…”

Perivascular adipose tissue in the pathogenesis of cardiovascular disease

“…Также в патогенезе аневризматической дегенерации аорты лежат инфильтрация воспалительными клетками, разрушение эластина и коллагена матриксными металлопротеиназами, вырабатываемыми макрофагами, некроз гладкомышечных клеток и патологический ангиогенез, что в совокупности приводит к истончению стенки сосуда. Таким образом, развитие аневризмы аорты рассматривается как совокупность дегенеративных процессов вкупе с неблагоприятным ремоделированием в сосудистой стенке [30]. Закономерно, что дисфункциональная жировая ткань путем усиления оксидативного стресса, выработки провоспалительных цитокинов и усиления гипоперфузии вносит значительную долю в патологический процесс.…”