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在心包内递送载有血管紧张素转换酶(ACE)抑制肽的微胶囊作为实验性急性心肌梗死模型中有前景的干细胞治疗载体

Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model.

作者信息

Báez-Díaz Claudia, Blanco-Blázquez Virginia, Sánchez-Margallo Francisco Miguel, López Esther, Martín Helena, Espona-Noguera Albert, Casado Javier G, Ciriza Jesús, Pedraz José Luis, Crisóstomo Verónica

机构信息

CIBERCV, Instituto de Salud Carlos III, 28029 Madrid, Spain.

Fundación Centro de Cirugía de Mínima Invasión Jesús Usón, 10071 Cáceres, Spain.

出版信息

Pharmaceutics. 2021 Nov 1;13(11):1824. doi: 10.3390/pharmaceutics13111824.

Abstract

The administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-l-lysine-alginate (APA) could increase cell survival and adherence. The intrapericardial (IP) approach potentially achieves high concentrations of the therapeutic agent in the infarcted area. We aimed to evaluate IP therapy using a saline vehicle as a control (CON), a dose of 30 × 10 CDCs (CDCs) or APA microcapsules containing 30 × 10 CDCs (APA-CDCs) at 72 h in a porcine AMI model. Magnetic resonance imaging (MRI) was used to determine the left ventricular ejection fraction (LVEF), infarct size (IS), and indexed end diastolic and systolic volumes (EDVi; ESVi) pre- and 10 weeks post-injection. Programmed electrical stimulation (PES) was performed to test arrhythmia inducibility before euthanasia. Histopathological analysis was carried out afterwards. The IP infusion was successful in all animals. At 10 weeks, MRI revealed significantly higher LVEF in the APA-CDC group compared with CON. No significant differences were observed among groups in IS, EDVi, ESVi, PES and histopathological analyses. In conclusion, the IP injection of CDCs (microencapsulated or not) was feasible and safe 72 h post-AMI in the porcine model. Moreover, CDCs APA encapsulation could have a beneficial effect on cardiac function, reflected by a higher LVEF at 10 weeks.

摘要

急性心肌梗死(AMI)后给予心肌球衍生细胞(CDC)很有前景。将CDC封装在海藻酸钠-聚-L-赖氨酸-海藻酸钠(APA)中可提高细胞存活率和黏附性。心包内(IP)给药途径有可能在梗死区域实现治疗剂的高浓度。我们旨在评估在猪AMI模型中,于72小时时使用生理盐水作为对照(CON)、一剂30×10个CDC(CDC组)或含有30×10个CDC的APA微胶囊(APA-CDC组)进行IP治疗的效果。使用磁共振成像(MRI)来确定注射前及注射后10周的左心室射血分数(LVEF)、梗死面积(IS)以及舒张末期和收缩末期容积指数(EDVi;ESVi)。在安乐死之前进行程序电刺激(PES)以测试心律失常的诱导性。之后进行组织病理学分析。所有动物的IP输注均成功。在10周时,MRI显示APA-CDC组的LVEF显著高于CON组。在IS、EDVi、ESVi、PES和组织病理学分析中,各组之间未观察到显著差异。总之,在猪模型中,AMI后72小时IP注射CDC(无论是否微囊化)是可行且安全的。此外,CDC的APA封装可能对心脏功能有有益影响,这在10周时较高的LVEF中得到体现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/8626005/96cb26a2dd2d/pharmaceutics-13-01824-g001.jpg

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