Abstract
BackgroundAbdominal aortic aneurysm (AAA) is life-threatening, surgical treatment is currently the only clinically available intervention for the disease. Mesenchymal stem cells (MSCs) have presented eligible immunomodulatory and regenerative abilities which showed favorable therapeutic efficacy in various cardiovascular diseases. However, current evidence summarizing the effectiveness of MSCs for AAA is lacking. Thus, a meta-analysis and systematic review was necessary to be performed to assess the therapeutic efficacy of MSCs for AAA in preclinical studies.MethodsComprehensive literature search restricted in English was conducted in PubMed, Cochrane Library, EBSCO, EMBASE and Web of Science from inception to Oct 2021. The primary outcomes were parameters about aortic diameter change during MSCs intervention. The secondary outcomes included elastin content and expression level of inflammatory cytokines, matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). Data were extracted and analyzed independently by two authors. The meta package with random effects model was used to calculate the pooled effect size and 95% confidence intervals in R (version 4.0.2).ResultsMeta-analysis of 18 included studies demonstrated that MSCs intervention has significant therapeutic effects on suppressing aortic diameter enlargement compared with the control group (diameter, SMD = − 1.19, 95% CI [− 1.47, − 0.91]; diameter change ratio, SMD = − 1.36, 95% CI [− 1.72, − 1.00]). Subgroup analysis revealed differences between MSCs and control group regarding to cell type, intervention route and cell compatibility. Moreover, the meta-analysis also showed that MSCs intervention had a significant effect on preserving aortic elastin content, reducing MCP-1, TNF-α, IL-6, MMP-2/9 and increasing TIMP-1/2 expression level compared with control group.ConclusionOur results suggested that MSC intervention is effective in AAA by suppressing aortic diameter enlargement, reducing elastin degradation, and modulating local immunoinflammatory reactions. These results are important for the systemic application of MSCs as a potential treatment candidate for AAA in further animal experiments and clinical trials.
Highlights
Abdominal aortic aneurysm (AAA) is permanent pathologic dilatation of the abdominal aorta, of which the maximum diameter of lesion area is 1.5 folds greater than the normal segment or more than 3 cm regardless of differences in patient gender and stature [1, 2]
13 studies were implemented with mice including 6 studies with ApoE-/- mice [26,27,28, 30, 31, 35], 6 studies with C57BL/6 mice [15, 21,22,23,24,25] and 1 study with SCID mice [29], 5 studies were implemented with rats including 4 studies with Fisher rats [32,33,34, 36] and 1 study with standard deviation (SD) rats [16]
Meta analysis of five studies including 8 experimental arms with random effects model showed Mesenchymal stem cell (MSC) significantly attenuated IL-6 expression level compared with control group (SMD = − 2.10, 95% confidence interval (CI) [− 3.38, − 0.82]) (Additional file 21: Fig. S19)
Summary
Abdominal aortic aneurysm (AAA) is permanent pathologic dilatation of the abdominal aorta, of which the maximum diameter of lesion area is 1.5 folds greater than the normal segment or more than 3 cm regardless of differences in patient gender and stature [1, 2]. The pathogenesis of AAA mainly includes infiltration of inflammatory cells such as macrophages, lymphocytes and neutrophils, degradation of the extracellular matrix mediated by matrix metalloproteinases, as well as apoptosis and phenotypic transition of medial vascular smooth muscle cells (VSMCs) [5, 6]. Cellular therapies, especially those based on mesenchymal stem cells (MSCs), have recently demonstrated inspiring repair capabilities in diseases such as spinal cord injury [7], cardiovascular diseases [8,9,10], and Crohn’s disease [11, 12]. A meta-analysis and systematic review was necessary to be performed to assess the therapeutic efficacy of MSCs for AAA in preclinical studies
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