Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model.
Claudia Báez-DíazVirginia Blanco-BlázquezFrancisco M Sánchez MargalloEsther LópezHelena MartínAlbert Espona-NogueraJavier G CasadoJesús CirizaJosé Luis PedrazVeronica CrisostomoPublished in: Pharmaceutics (2021)
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 × 106 CDCs (CDCs) or APA microcapsules containing 30 × 106 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.
Keyphrases
- acute myocardial infarction
- left ventricular
- magnetic resonance imaging
- ejection fraction
- cell therapy
- aortic stenosis
- percutaneous coronary intervention
- contrast enhanced
- hypertrophic cardiomyopathy
- heart failure
- cardiac resynchronization therapy
- left atrial
- blood pressure
- stem cells
- mitral valve
- spinal cord injury
- gestational age
- computed tomography
- low dose
- ultrasound guided
- coronary artery disease
- skeletal muscle
- cell cycle arrest
- insulin resistance
- acute coronary syndrome
- atrial fibrillation
- replacement therapy
- preterm birth