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Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction.

ABSTRACT: Objective: We investigated the potency of cardiac repair based on echocardiography-guided multiple percutaneous left ventricular intramyocardial injection of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) after myocardial infarction (MI). Methods: Mice with surgically induced MI were randomly divided into three groups (n = 8 in each group) and subjected to echocardiography-guided percutaneous left ventricular infarcted border injection of hiPSC-CMs (single dose; 10 μl 3 × 10⁵ cells) or repeated injections of hiPSC-CMs at post-MI weeks 1 and 2 (multiple doses). The sham group of animals underwent all surgical procedures necessary for MI induction except for ligation. Then 4 weeks after MI, heart function was measured with transthoracic echocardiography. Engraftment was evaluated through the detection of human-specific cardiac troponin T. Infarct size and collagen volume were calculated with Sirius Red/Fast Green staining. Angiogenesis was evaluated with isolectin B4 staining. Cardiac remodeling was evaluated from the cardiomyocyte minimal fiber diameter in the infarcted border zone. Apoptosis was detected via TdT-mediated dUTP Nick-End Labeling (TUNEL) staining in cardiomyocytes from the infarcted border zone. Results: No mice died after echocardiography-guided percutaneous left ventricular intramyocardial injection. hiPSC-CMs were about nine-fold higher in the multiple-dose group at week 4 compared to the single-dose group. Multiple-dose transplantation was associated with significant improvement in left ventricular function, infarct size, angiogenesis, cardiac remodeling, and cardiomyocyte apoptosis. Conclusion: Echocardiography-guided multiple percutaneous left ventricular intramyocardial injection is a feasible, satisfactory, repeatable, relatively less invasive, and effective method of delivering cell therapy. The delivery of hiPSC-CMs indicates a novel therapy for MI.

SUBMITTER: Wu X

PROVIDER: S-EPMC8600116 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEchocardiography-guided percutaneous intramyocardial alginate-hydrogel implantation (PIMAHI) is a novel treatment approach for heart failure (HF). We validated PIMAHI safety and efficacy in canine HF models.MethodsFourteen canines with HF [produced by coronary artery ligation, left ventricular ejection fraction (LVEF) < 35%] were randomised to PIMAHI treatment (n = 8) or controls (n = 6). Echocardiography, two-dimensional speckle tracking echocardiography, and pathological examinations after a 6-month follow-up were performed. Repeated-measures analysis of variance was used for within-group comparisons.ResultsAt 6-month follow-up, PIMAHI treatment reversed LV dilation and remodelling, increasing LV free wall thickness (LVFW, p = 0.002) and interventricular septum thickness (IVS, p < 0.001) and reducing LV end-diastolic volume (EDV, p = 0.008) and end-systolic volume (ESV, p = 0.004). PIMAHI significantly improved LV systolic function, increasing LVEF (EF, p = 0.004); enhanced LV myocardial contractility, including increased LV global longitudinal strain (GLS, p < 0.001), global circumferential strain (GCS, p = 0.006), and mitral annulus displacement (MAD, p = 0.001). Compared with controls at 6-month, PIMAHI group significantly increased LVFW thickness (8.5 ± 0.3 vs. 6.8 ± 0.2 mm, p = 0.002) and IVS (7.9 ± 0.1 vs. 6.1 ± 0.2 mm, p < 0.001); decreased LVEDV (30.1 ± 1.6 vs. 38.9 ± 4.5 ml, p = 0.049) and ESV (17.3 ± 1.2 vs. 28.7 ± 3.6 ml, p = 0.004); increased LV systolic function (42.7 ± 1.5 vs. 26.7 ± 1.1% in EF, p = 0.001); and enhanced LV myocardial contractility including GLS (13.5 ± 0.8 vs. 8.4 ± 0.6%, p = 0.002), GCS (16.5 ± 1.4 vs. 9.2 ± 0.6%, p = 0.001), and MAD (11.4 ± 3.5vs 4.6 ± 2.5 mm, p = 0.003). During PIMAHI treatment, no sustained arrhythmia, pericardial, or pleural effusion occurred.ConclusionsPIMAHI in canine HF models was safe and effective. It reversed LV dilation and improved LV function.

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Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction.

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