Liang Xiaoting, Liu Jing, Li Mimi, Lin Fang, Zhuang Rulin, Meng Qingshu, Ma Xiaoxue, Xin Yuanfeng, Gong Xin, He Zhiying, Han Wei, Zhou Xiaohui, Liu Zhongmin
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China.
Stem Cells Int. 2023 Mar 17;2023:6256115. doi: 10.1155/2023/6256115. eCollection 2023.
Overactive inflammatory responses contribute to progressive cardiac dysfunction after myocardial infarction (MI). Mesenchymal stem cell (MSC) has generated significant interest as potent immune modulators that can regulate excessive immune responses. We hypothesized that intravenous (iv) administration of human umbilical cord-derived MSC (HucMSC) exerts systemic and local anti-inflammation effects, leading to improved heart function after MI. In murine MI models, we confirmed that single iv administration of HucMSC (30 × 10) improved cardiac performance and prevented adverse remodeling after MI. A small proportion of HucMSC is trafficked to the heart, preferentially in the infarcted region. HucMSC administration increased CD3 T cell proportion in the periphery while decreased T cell proportion in both infarcted heart and mediastinal lymph nodes (med-LN) at 7-day post-MI, indicating a systematic and local T cell interchange mediated by HucMSC. The inhibitory effects of HucMSC on T cell infiltration in the infarcted heart and med-LN sustained to 21-day post-MI. Our findings suggested that iv administration of HucMSC fostered systemic and local immunomodulatory effects that contributed to the improvement of cardiac performance after MI.
过度活跃的炎症反应会导致心肌梗死（MI）后进行性心脏功能障碍。间充质干细胞（MSC）作为一种能够调节过度免疫反应的有效免疫调节剂，已引起了广泛关注。我们推测，静脉注射人脐带间充质干细胞（HucMSC）可发挥全身和局部抗炎作用，从而改善心肌梗死后的心脏功能。在小鼠心肌梗死模型中，我们证实单次静脉注射HucMSC（30×10）可改善心脏功能，并预防心肌梗死后的不良重塑。一小部分HucMSC会迁移至心脏，优先聚集在梗死区域。在心肌梗死后7天，注射HucMSC可增加外周血中CD3 T细胞比例，同时降低梗死心脏和纵隔淋巴结（med-LN）中的T细胞比例，这表明HucMSC介导了系统性和局部性T细胞交换。HucMSC对梗死心脏和med-LN中T细胞浸润的抑制作用持续至心肌梗死后21天。我们的研究结果表明，静脉注射HucMSC可产生全身和局部免疫调节作用，有助于改善心肌梗死后的心脏功能。
