Gan Yang, Wang Changyi, Liao Ruili, Zhang Pei, Nie Yongmei, Yu Fengxu, Wan Juyi, Liao Bin, Mao Liang, Liu Hui, Fu Yong
Department of cardiothoracic surgery, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, 620000, China.
Department of Cardiovascular Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Mol Cell Biochem. 2025 Apr 1. doi: 10.1007/s11010-025-05273-4.
Mesenchymal stem cells (MSCs) have been shown to attenuate myocardial fibrosis after myocardial infarction by secreting various bioactive molecules that positively affect the failing heart. We hypothesized that serum factors play an active role in the activation of bone marrow MSCs after myocardial infarction and explored the effect of differential exocytosis on cardiac repair after infarct serum preconditioning by examining whether exosomes derived from MSCs have a positive effect on cardiac fibrosis. Bone marrow MSCs were pretreated by collecting rat myocardial infarction serum, followed by the collection of myocardial infarction serum exosomes (MIS-EXO). In vivo, intramyocardial injection of exosomes was performed 30 min after permanent ligation of the anterior descending branches of Sprague Dawley rats, and echocardiography was performed at different time intervals to evaluate cardiac function. Hearts were sampled 4 weeks later, and the degree of myocardial fibrosis and inflammatory response were evaluated using hematoxylin and eosin and Masson's trichrome staining. Treatment with common culture-derived exosomes (CON-EXO) improved cardiac function and myocardial fibrosis after myocardial infarction in rats compared with the myocardial infarction group. In vitro, the antifibrotic effects of different exosomes on tumor growth factor-β-induced fibroblast fibrosis model were assessed by protein blotting, qPCR, and immunofluorescence. Compared with CON-EXO, MIS-EXO exerted superior therapeutic effects in terms of anti-inflammation, improvement of left ventricular function, and reduction of fibrosis. Infarct serum pretreatment with bone marrow mesenchymal stem cell-derived exosomes enhances the anti-cardiac fibrosis effect in rats after myocardial infarction.
间充质干细胞（MSCs）已被证明可通过分泌各种对衰竭心脏有积极影响的生物活性分子来减轻心肌梗死后的心肌纤维化。我们假设血清因子在心肌梗死后骨髓间充质干细胞的激活中起积极作用，并通过检查间充质干细胞来源的外泌体是否对心脏纤维化有积极影响，探讨梗死血清预处理后差异外排对心脏修复的作用。通过收集大鼠心肌梗死血清预处理骨髓间充质干细胞，随后收集心肌梗死血清外泌体（MIS-EXO）。在体内，在Sprague Dawley大鼠前降支永久结扎30分钟后进行心肌内注射外泌体，并在不同时间间隔进行超声心动图检查以评估心脏功能。4周后取心脏样本，使用苏木精-伊红和Masson三色染色评估心肌纤维化程度和炎症反应。与心肌梗死组相比，用普通培养来源的外泌体（CON-EXO）治疗可改善大鼠心肌梗死后的心脏功能和心肌纤维化。在体外，通过蛋白质印迹、qPCR和免疫荧光评估不同外泌体对肿瘤生长因子-β诱导的成纤维细胞纤维化模型的抗纤维化作用。与CON-EXO相比，MIS-EXO在抗炎、改善左心室功能和减少纤维化方面具有更好的治疗效果。骨髓间充质干细胞来源的外泌体进行梗死血清预处理可增强大鼠心肌梗死后的抗心脏纤维化作用。
