Mesenchymal stem cells (MSCs), are multipotent adult somatic cells that are able to differentiate into a variety of cell types including osteoblasts, chondrocytes and adipocytes. These multipotent properties mean MSCs can be applied in the treatment of a variety of diseases; examples include therapies for sepsis and experimental colitis that have taken advantage of the anti-inflammatory effects of MSCs.
Yuji Narita and colleagues from Nagoya University Graduate School of Medicine, Japan have already demonstrated that the anti-inflammatory effects of bone marrow-derived MSCs (BM-MSCs) can slow the development of aortic aneurysm in a mouse model for atherosclerosis, when implanted intra-abdominally via laparotomy. In patients with aortic aneurysm, a condition where the aorta swells to potentially life-threatening extents and which is associated with atherosclerosis, this surgical approach may be too invasive. Consequently, in a recent study published in the Journal of Translational Medicine, Narita and colleagues investigated whether the same beneficial effects can be achieved through intravenous delivery of BM-MSCs.
Aortic aneurysms were induced in apolipoprotein E-deficient (apoE−/−) mice, which are known to rapidly develop atherosclerosis, by angiotensin II infusion for 28 days. The mice then received either weekly intravenous administrations of BM-MSCs, isolated from the femurs and tibiae of apoE−/− mice, or saline. The formation incidence of aortic aneuryms, aortic diameter, macrophage accumulation, matrix metalloproteinase activity, elastin content, and cytokines were all evaluated after four weeks.
The authors observed a significant decrease in aortic diameter in the BM-MSC-treated mice, which was associated with decreased macrophage infiltration and suppressed activities of MMP-2 and MMP-9 in aortic tissues, as well as a preservation of elastin content of aortic tissues. Levels of cytokines interleukin-1β and -6, and monocyte chemotactic protein-1 were also significantly decreased in the aortic tissues of BM-MSC-treated mice, while levels of insulin-like growth factor-1 and tissue inhibitor of metalloproteinases-2 had increased these tissues.
The study suggests that that multiple systemic injections of BM-MSCs are effective in suppressing inflammation in angiotensin II-infused apoE−/− mice, and moreover inhibit the development of aortic aneurysms. Intravenous delivery of BM-MSCs may therefore offer a simpler and less invasive alternative to implantation in the treatment of aortic aneurysms, as well as providing a more consistently repeatable method for administering a large number of cells. The ability of BM-MSCs to home in to sites of tissue damage or inflammation mean this method may have potential as a therapy in patients with aortic aneurysm.
Intravenous administration of mesenchymal stem cells prevents angiotensin II-induced aortic aneurysm formation in apolipoprotein E-deficient mouse
Journal of Translational Medicine 2013, 11:175
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