Mesenchymal stem cell–derived conditioned medium attenuate angiotensin II‐induced aortic aneurysm growth by modulating macrophage polarization

Abstract

Mesenchymal stem cells (MSCs) exhibit therapeutic benefits on aortic aneurysm (AA); however, the molecular mechanisms are not fully understood. The current study aimed to investigate the therapeutic effects and potential mechanisms of murine bone marrow MSC (BM‐MSCs)–derived conditioned medium (MSCs‐CM) on angiotensin II (AngII)‐induced AA in apolipoprotein E‐deficient (apoE−/−) mice. Murine BM‐MSCs, MSCs‐CM or control medium were intravenously administrated into AngII‐induced AA in apoE−/− mice. Mice were sacrificed at 2 weeks after injection. BM‐MSCs and MSCs‐CM significantly attenuated matrix metalloproteinase (MMP)‐2 and MMP‐9 expression, aortic elastin degradation and AA growth at the site of AA. These treatments with BM‐MSCs and MSCs‐CM also decreased Ly6chigh monocytes in peripheral blood on day 7 and M1 macrophage infiltration in AA tissues on day 14, whereas they increased M2 macrophages. In addition, BM‐MSCs and MSCs‐CM reduced MCP‐1, IL‐1Ra and IL‐6 expression and increased IL‐10 expression in AA tissues. In vitro, peritoneal macrophages were co‐cultured with BM‐MSCs or fibroblasts as control in a transwell system. The mRNA and protein expression of M2 macrophage markers were evaluated. IL‐6 and IL‐1β were reduced, while IL‐10 was increased in the BM‐MSC systems. The mRNA and protein expression of M2 markers were up‐regulated in the BM‐MSC systems. Furthermore, high concentration of IGF1, VEGF and TGF‐β1 was detected in MSCs‐CM. Our results suggest that MSCs‐CM could prevent AA growth potentially through regulating macrophage polarization. These results may provide a new insight into the mechanisms of BM‐MSCs in the therapy of AA.

Trans-portal hepatic infusion of cultured bone marrow-derived mesenchymal stem cells in a steatohepatitis murine model

“…Reports have shown that a reduction in M1 macrophages and an increase in M2 macrophages improved liver fibrosis both in vivo and in vitro by suppressing the inflammatory cytokines, interleukin (IL)-6 and IL-1b, releasing the antifibrotic factor IL-10, inhibiting the activity of hepatic stellate cells, and increasing the levels of the extracellular matrix degrading enzymes, such as matrix metalloproteinase (MMP)-9 and MMP-12. (22)(23)(24)(25) Griess et al (26) have also reported that M2 macrophages increased the levels of SOD-2, a protein effective against oxidative stress, suggesting that, in the present study, increased M2 macrophages caused an increase in SOD-2 protein, which controlled intrahepatic oxidative stress, thereby reducing the number of 8-OHdG-positive cells in the liver.…”

The therapeutic potential of mesenchymal stem cells for cardiovascular diseases

“…A large number of clinical trials should be conducted to determine the optimal MSC dose and delivery route to improve the survival rate of patients with MI and lay the foundation for solving other problems 78,79 . In addition to their effect in MI, MSCs and MSC-derived extracellular vesicles have important effects on other CVDs, such as aortic aneurysm and atherosclerosis [80][81][82][83][84] .…”

A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy

“…The western blotting analysis was performed as previously described 28 . Briefly, cells/aortic tissue were harvested and homogenized on ice with RIPA (Beyotime Biotechnology P0013B) containing proteinase inhibitor (Complete, EDTA-free protease inhibitor cocktail Tablets provided in EASY pack, Roche, 04 693 132 001).…”