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

Xun Wu,Jinfu Yang,Kun Xiang,Jun Peng,Jianjun Guo,Qing Guan,Weijie Tang,Kele Qin,Yuanjing Zhou,Chengming Fan,Chukwuemeka Daniel Iroegbu,Di Wang

doi:10.3389/fcvm.2021.768873

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.

Highlights

The leading cause of death from coronary heart disease worldwide is acute myocardial infarction (MI) [1]
We explored whether multiple injections of cells could significantly increase the number of transplanted cells, reduce the area of cardiac scar tissue, and improve cardiac function compared to a single injection of cells, providing a new strategy for the clinical application of multiple injections of cells
HiPSC-CMs were digested with cardiomyocyte dissociation medium and resuspended in the culture medium, which had been preserved in a 37◦C water bath

Summary

Introduction

The leading cause of death from coronary heart disease worldwide is acute myocardial infarction (MI) [1]. Myocardial cells in the infarcted area die quickly when ischemia and hypoxia occur. The injured heart tissue becomes scar tissue, which has few mechanical or electrical properties and compromises cardiac function. Cardiac regeneration in the mammalian adult heart is very limited. The viable myocardium is not enough to maintain sufficient cardiac output, which may eventually lead to heart failure [2]. Organ shortages, severe postoperative complications, and the side effects of long-term immunosuppressive therapy limit the use of these therapies [5]. Early treatment of MI is of great importance, and the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is considered a promising method of repairing the damaged heart

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Discussion

Conclusion