Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes After Myocardial Infarction

Objective: To investigate the cardiac repair potency with echocardiography-guided multiple percutaneous left ventricular intramyocardial injection of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) after myocardial infarction. Methods: The surgically induced myocardial infarcted mice were randomly divided into three groups (8 in each) and were injected with echocardiography-guided percutaneous left ventricular infarcted border zone of one shot hiPSC-CMs (single dose, 10ul of 3x10 5 cells), medium, or repeated delivery of hiPSC-CMs at post-MI week 1 and 2 (multiple dose). The sham group of animals underwent all surgical procedures necessary for MI induction except for the ligation step. 4 weeks after the MI, heart function was measured by the transthoracic echocardiography. The engraftment size was evaluated through the detection of human specific cardiac troponin T. Infarcted size and collagen volume were calculated by sirius-red and fast green staining. Angiogenesis was evaluated by the staining of isolectin B4. Cardiac remodeling was evaluated by the cardiomyocyte minimal fiber diameter in the infarcted border zone. Apoptosis was detected via tunel staining in cardiomyocyte from the infarcted border zone. Results: No death was detected with echocardiography-guided percutaneous left ventricular intramyocardial injection. The number of hiPSC-CMs was about 9-fold higher in multiple dose group at week 4 compaired to single dose group. The multiple dose transplantation was associated with significant improvement in left ventricular function, infarct size, angiogenesis, cardiac remodeling, and cardiomyocyte apoptosis. Conclusions: Echocardiography-guided multiple percutaneous left ventricular intramyocardial injection is a feasible, satisfactory, repeatable, relatively less invasive and effective delivery method for cell therapy and the delivery of hiPSC-CMs indicate a novel therapy for myocardial infarction.