Fundación Centro de Cirugía de Mínima Invasión Jesús Usón, Carretera N-521, km 41, 10071, Cáceres, Spain.
CIBERCV, Instituto de Salud Carlos III, Madrid, Spain.
Sci Rep. 2021 Nov 12;11(1):22155. doi: 10.1038/s41598-021-01728-y.
The epicardial administration of therapeutics via the pericardial sac offers an attractive route, since it is minimally invasive and carries no risks of coronary embolization. The aim of this study was to assess viability, safety and effectiveness of cardiosphere-derived cells (CDCs), their extracellular vesicles (EVs) or placebo administered via a mini-thoracotomy 72 h after experimental infarction in swine. The epicardial administration was completed successfully in all cases in a surgery time (knife-to-skin) below 30 min. No significant differences between groups were found in cardiac function parameters evaluated using magnetic resonance imaging before therapy and at the end of the study, despite a trend towards improved function in CDC-treated animals. Moreover, infarct size at 10 weeks was smaller in treated animals, albeit not significantly. Arrhythmia inducibility did not differ between groups. Pathological examination showed no differences, nor were there any pericardial adhesions evidenced in any case 10 weeks after surgery. These results show that the epicardial delivery of CDCs or their EVs is safe and technically easy 3 days after experimental myocardial infarction in swine, but it does not appear to have any beneficial effect on cardiac function. Our results do not support clinical translation of these therapies as implemented in this work.
通过心包腔在心外膜给药是一种有吸引力的途径，因为它是微创的，并且不存在冠状动脉栓塞的风险。本研究的目的是评估细胞外囊泡（EVs）或安慰剂给药的可行性、安全性和有效性，这些细胞外囊泡或安慰剂是通过迷你开胸术在实验性心肌梗死发生后 72 小时在猪体内给药的。在所有病例中，手术时间（刀皮时间）均在 30 分钟以下，成功完成了心外膜给药。尽管在接受 CDC 治疗的动物中，心脏功能参数有改善的趋势，但在治疗前和研究结束时使用磁共振成像评估的心脏功能参数在各组之间没有发现显著差异。此外，在 10 周时，治疗动物的梗死面积较小，但无统计学意义。心律失常的诱导率在各组之间没有差异。病理检查也没有发现差异，并且在手术后 10 周的任何情况下都没有发现心包粘连的证据。这些结果表明，在猪实验性心肌梗死后 3 天，通过心包腔给予细胞外囊泡或其 EVs 是安全的，技术上也很容易，但对心脏功能似乎没有任何有益的影响。我们的结果不支持在本研究中实施的这些治疗方法的临床转化。
