Acute myocardial infarction triggers a strong inflammatory response in the affected cardiac tissue. New therapeutic tools based on stem cell therapy may modulate the unbalanced inflammation in the damaged cardiac tissue, contributing to the resolution of this pathological condition. The main goal of this study was to analyze the immunomodulatory effects of cardiosphere-derived cells (CDCs) and their extracellular vesicles (EV-CDCs), delivered by intrapericardial administration in a clinically relevant animal model, during the initial pro-inflammatory phase of an induced myocardial infarction. This effect was assessed in peripheral blood and pericardial fluid leukocytes from infarcted animals. Additionally, cardiac functional parameters, troponin I, hematological and biochemical components were also analyzed to characterize myocardial infarction-induced changes, as well as the safety aspects of these procedures. Our preclinical study demonstrated a successful myocardial infarction induction in all animals, without any reported adverse effect related to the intrapericardial administration of CDCs or EV-CDCs. Significant changes were observed in biochemical and immunological parameters after myocardial infarction. The analysis of peripheral blood leukocytes revealed an increase of M2 monocytes in the EV-CDCs group, while no differences were reported in other lymphocyte subsets. Moreover, arginase-1 (M2-differentiation marker) was significantly increased in pericardial fluids 24 h after EV-CDCs administration. In summary, we demonstrate that, in our experimental conditions, intrapericardially administered EV-CDCs have an immunomodulatory effect on monocyte polarization, showing a beneficial effect for counteracting an unbalanced inflammatory reaction in the acute phase of myocardial infarction. These M2 monocytes have been defined as “pro-regenerative cells” with a pro-angiogenic and anti-inflammatory activity.

中文翻译：

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从心球来源的细胞向细胞外囊泡的心内膜递送在猪心肌梗死急性期可刺激M2极化。

急性心肌梗塞在受影响的心脏组织中引发强烈的炎症反应。基于干细胞疗法的新治疗工具可能会调节受损心脏组织中的不平衡炎症，有助于缓解这种病理状况。这项研究的主要目的是分析在临床相关的动物模型中，由心包内给药在临床相关的动物模型中，心包膜来源的细胞（CDC）及其细胞外囊泡（EV-CDC）的免疫调节作用。诱发心肌梗塞。在来自梗塞动物的外周血和心包积液中评估了这种作用。此外，心脏功能参数肌钙蛋白I，还分析了血液和生化成分，以表征心肌梗死引起的变化以及这些程序的安全性。我们的临床前研究表明，在所有动物中均成功诱导了心肌梗塞，没有任何与心内注射CDC或EV-CDC相关的不良反应的报道。观察到心肌梗塞后生化和免疫学指标发生了显着变化。外周血白细胞分析显示，EV-CDCs组中M2单核细胞增加，而其他淋巴细胞亚群则无差异。此外，在施用EV-CDC后24小时，心包液中的精氨酸酶-1（M2分化标记）显着增加。总而言之，我们证明了在我们的实验条件下，心包内施用的EV-CDC对单核细胞极化具有免疫调节作用，显示出在心肌梗塞急性期抵抗不平衡炎症反应的有益作用。这些M2单核细胞已被定义为具有促血管生成和抗炎活性的“促再生细胞”。