化疗引起的心脏毒性以及随后的心力衰竭（HF）是全世界癌症幸存者发病和死亡的主要原因。化疗引起的心力衰竭极具挑战性，因为它通常出现在通常不适合左心室装置植入或心脏移植的患者中。为了探索化疗引起心力衰竭的癌症幸存者的替代治疗策略，我们开发了一种微创可输注心脏基质细胞分泌体粘合剂（MISA），可以通过内窥镜引导心包内注射进行局部递送。为了模拟老年患者化疗引起心力衰竭的典型临床表现，我们建立了老年大鼠模型，通过连续注射阿霉素诱导限制性心肌病并发心力衰竭。在体外，我们证明 MISA 不仅可以增强心肌细胞的增殖能力和活力，还可以抑制其凋亡。在体内，我们证明 MISA 可改善心室收缩指数，并通过促进心肌细胞增殖、血管生成和线粒体呼吸，对限制性心肌病的组织学和结构特征产生有益影响。此外，我们还在具有完整免疫系统的健康猪模型中评估了 MISA 心包内递送的安全性和可行性。总的来说，我们的数据表明，MISA 具有巨大的潜力，可以转化为大型动物模型，并最终在心脏移植的最终选择之前应用于化疗引起的心力衰竭。© 2024 作者。

Chemotherapy-induced cardiotoxicity with subsequent heart failure (HF) is a major cause of morbidity and mortality in cancer survivors worldwide. Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation. To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF, we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive (MISA) that could be delivered locally through an endoscope-guided intrapericardial injection. To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients, we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections. In vitro, we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability, but also inhibited their apoptosis. In vivo, we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation, angiogenesis, and mitochondrial respiration. Additionally, we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system. In general, our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.© 2024 The Authors.