骨髓间充质干细胞通过上调脾调节性 T 细胞减轻心肌缺血再灌注损伤。
Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia-reperfusion injury via upregulation of splenic regulatory T cells.
机构信息
Department of Emergency, Zhejiang Provincial People's Hospital,People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
Department of Health Management Center, Zhejiang Provincial People's Hospital,People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
出版信息
BMC Cardiovasc Disord. 2021 Apr 27;21(1):215. doi: 10.1186/s12872-021-02007-4.
BACKGROUND
Myocardial ischemia-reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined.
METHODS
We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses.
RESULTS
CD25Foxp3 regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p < 0.01). This was accompanied by upregulation of interleukin 10 and transforming growth factor β1 and downregulation of creatinine kinase and lactate dehydrogenase in the serum. The post-MIRI mice receiving BM-MSCs showed attenuated inflammation and cellular apoptosis in the heart. Meanwhile, splenectomy compromised all therapeutic effects of BM-MSCs.
CONCLUSION
Administration of BM-MSCs effectively alleviates MIRI in mice through inducing Treg activation, particularly in the spleen.
背景
心肌缺血再灌注损伤（MIRI）是心肌梗死等心血管疾病的主要病理表现。骨髓间充质干细胞（BM-MSCs）的潜在治疗效果以及调节性 T 细胞（Tregs）在 MIRI 中的参与作用仍有待确定。
方法
我们使用左冠状动脉升支缺血诱导的实验性急性 MIRI，随后将其随机分为 IgG 或抗 CD25 抗体 PC61 组，并分别联合或不联合静脉注射 BM-MSCs。实验性 MIRI 前进行脾切除术，随后静脉注射 BM-MSCs。在 MIRI 后 72 小时，采集心脏和脾脏进行细胞和组织学分析。
结果
与相应的对照组相比，接受 IgG+BM-MSCs 和 PC61+BM-MSCs 的 MIRI 后，小鼠心脏和脾脏中的 CD25Foxp3 调节性 T 细胞明显升高（均 p<0.01）。这伴随着血清中白细胞介素 10 和转化生长因子β1 的上调以及肌酸激酶和乳酸脱氢酶的下调。接受 BM-MSCs 的 MIRI 后小鼠心脏的炎症和细胞凋亡减轻。同时，脾切除术削弱了 BM-MSCs 的所有治疗效果。
结论
BM-MSCs 通过诱导 Treg 激活，特别是在脾脏中，有效缓解了小鼠的 MIRI。
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