Therapeutic effect of allogeneic bone marrow–derived mesenchymal stromal cells on aortic aneurysms

• Published in: Cell and tissue research Vol. 383; no. 2; pp. 781 - 793
• Main Authors: Akita, Naohiro, Narita, Yuji, Yamawaki-Ogata, Aika, Usui, Akihiko, Komori, Kimihiro
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2021; Springer; Springer Nature B.V
• Subjects: Analysis; Aneurysms; Angiotensin; Angiotensin II; Animal models; Animals; Anti-inflammatory agents; Aorta - enzymology; Aorta - pathology; Aortic Aneurysm - therapy; Aortic aneurysms; Apolipoprotein E; Apolipoproteins; Autografts; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cell Proliferation; Chemokines - metabolism; Elastin - metabolism; Enzymatic activity; Gelatinase A; Gelatinase B; Health aspects; Human Genetics; Immune response; Immune Tolerance; Inflammation; Insulin-like growth factor I; Interleukin 6; Intravenous administration; Lymphocytes; Lymphocytes - cytology; Macrophages - metabolism; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - immunology; Mesenchyme; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Medicine; Monocyte chemoattractant protein 1; Penicillin G; Proteolysis; Proteomics; Reactive Oxygen Species - metabolism; Regular Article; Stem cells; Stromal cells; Tissue inhibitor of metalloproteinase 2; Transplantation, Homologous; Allogeneic; Off-the-shelf; Mesenchymal stromal cells; Autologous; Cell therapy; Aortic aneurysm
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-020-03295-6

We previously reported the effectiveness of autologous mesenchymal stromal cells (MSCs) for the treatment of aortic aneurysm (AA), mediated mainly by these cells’ anti-inflammatory properties. In this study, we investigate whether the therapeutic effects of allogeneic MSCs on AA are the same as those of autologous MSCs. To examine the immune response to allogeneic MSCs, C57BL/6 lymphocytes were co-cultured with BALB/c MSCs for 5 days in vitro. Apolipoprotein E-deficient C57BL/6 mice with AA induced by angiotensin II were randomly divided into three groups defined by the following intravenous injections: (i) 0.2 ml of saline ( n  = 10, group S) as a control, (ii) 1 × 10 6 autologous MSCs (isolated from C57BL/6, n  = 10, group Au) and (iii) 1 × 10 6 allogeneic MSCs (isolated from BALB/c, n  = 10, group Al). Two weeks after injection, aortic diameters were measured, along with enzymatic activities of MMP-2 and MMP-9 and cytokine concentrations in AAs. Neither allogenic (BALB/c) MSCs nor autologous (C57BL/6) MSCs accelerated the proliferation of lymphocytes obtained from C57BL/6. Compared with group S, groups Au and Al had significantly shorter aortic diameters (group S vs Au vs Al; 2.29 vs 1.40 vs 1.36 mm, respectively, p  < 0.01), reduced MMP-2 and MMP-9 activities, downregulated IL-6 and MCP-1 and upregulated expression of IGF-1 and TIMP-2. There were no differences in these results between groups Au and Al. Thus, our study suggests that treatment with allogeneic MSCs improves chronic inflammation and reduced aortic dilatation. These effects were equivalent to those of autologous MSCs in established mouse models of AA.