Therapeutic Potential of Allogenic Bone Marrow-Derived Mesenchymal Stem Cells for Aortic Aneurysm

Abstract

Introduction - We have previously reported effectiveness of autologous bone marrow derived mesenchymal stem cells (BM-MSCs) for regression of aortic aneurysm (AA). However, they have various disadvantage in terms of cell quality and quantity. Meanwhile, it is known that the stem cell has ability of immunological tolerance. The purpose of this study were to investigate whether treatment of allogeneic MSCs is effective for angiotensin II (AT II)-induced apolipoprotein E-deficient (apoE−/−) already-formed AA mouse. Methods - To identify characterization of each MSCs, the surface markers were checked by flow cytometry. AA was induced in apoE−/− mice by Ang II-infusion for 28 days through subcutaneously implanted osmotic mini-pump. The mice were randomly divided into 3 groups: (ⅰ) 0.2ml saline was intra-veinously injected (n=10, group S), (ⅱ) 1 × 106 autologous BM-MSCs(isolated from C57BL/6) in 0.2 ml saline (n=10, group Au), (ⅲ) 1 × 106 allogeneic BM-MSCs (isolated from BALB/C) (n=10, group Al) via tail vein. Mice were sacrificed at 2weeks after injection. Aortic diameter, matrix metalloproteinase (MMP)-2 and -9 enzymatic activity and cytokine concentrations were measured in obtained aortic tissue. Results - Flow cytometric analysis demonstrated that the both MSCs were similar in surface markers .The Aortic diameters of group Au and Al were significantly decreased compared to group S (group S vs Au vs Al; 2.29 vs 1.40 vs 1.36 (mm), p<0.01). The enzymatic activities of MMP-2 and -9 were significantly reduced in both MSCs groups (active-MMP2: group S vs Au vs Al; 0.45 vs 0.28 vs 0.24 (unit/ml), p<0.05 amd active-MMP9: group S vs Au vs Al; 0.34 vs 0.16 vs 0.14 (unit/ml), p<0.05). Inflammatory cytokines were down-regulated in the both MSC groups (interleukin-6: group S vs Au vs Al; 3399.5 vs 1475.6 vs 937.5 (pg/ml), p<0.01 and monocyte chemotactic protein-1: group S vs Au vs Al; 352.7 vs 208.0 vs 165.1 (pg/m), p<0.05).Insulin-like growth factor (IGF)-1 and tissue inhibitor of metalloproteinase (TIMP)-2 were up-regulated in the MSC groups (IGF-1: group S vs Au vs Al; 2.0 vs 4.7 vs 5.7 (pg/ml), p<0.01; TIMP-2: group S vs Au vs Al; 4.0 vs 9.5 vs 11.1 (pg/ml), p<0.01). Both MSCs injection inhibited infiltration of M1 macrophages in the aortic tissue. Conclusion - Our results suggest that the therapeutic effect of allogeneic MSCs might be similar to that of autologous MSCs for treatment of AA. Allogeneic MSCs injection could provide an alternative therapeutic strategy for the treatment of AA.