Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Cell Tissue Res. 2021 Feb;383(2):781-793. doi: 10.1007/s00441-020-03295-6. Epub 2020 Nov 4.
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 autologous MSCs (isolated from C57BL/6, n = 10, group Au) and (iii) 1 × 10 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.
我们之前报道过自体间充质基质细胞(MSCs)治疗主动脉瘤(AA)的有效性,主要是通过这些细胞的抗炎特性介导的。在这项研究中,我们研究了同种异体 MSCs 对 AA 的治疗效果是否与自体 MSCs 相同。为了研究对同种异体 MSCs 的免疫反应,将 C57BL/6 淋巴细胞与 BALB/c MSCs 在体外共培养 5 天。用血管紧张素 II 诱导的载脂蛋白 E 缺陷型 C57BL/6 小鼠随机分为三组,通过以下静脉注射进行定义:(i)0.2ml 生理盐水(n=10,组 S)作为对照,(ii)1×10 个自体 MSCs(从 C57BL/6 分离,n=10,组 Au)和(iii)1×10 个同种异体 MSCs(从 BALB/c 分离,n=10,组 Al)。注射后 2 周,测量主动脉直径,以及 MMP-2 和 MMP-9 的酶活性和 AA 中的细胞因子浓度。同种异体(BALB/c)MSCs 和自体(C57BL/6)MSCs 均不会加速从 C57BL/6 获得的淋巴细胞的增殖。与组 S 相比,组 Au 和 Al 的主动脉直径明显更短(组 S 与 Au 与 Al 相比;2.29 与 1.40 与 1.36mm,分别,p<0.01),MMP-2 和 MMP-9 活性降低,IL-6 和 MCP-1 下调,IGF-1 和 TIMP-2 表达上调。组 Au 和 Al 之间的这些结果没有差异。因此,我们的研究表明,同种异体 MSCs 治疗可改善慢性炎症和减少主动脉扩张。这些效果在已建立的 AA 小鼠模型中与自体 MSCs 相当。