Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction
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...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:e49537715dfc478986c915353aece4c82021-11-04T07:22:06ZCardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction2297-055X10.3389/fcvm.2021.768873https://doaj.org/article/e49537715dfc478986c915353aece4c82021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.768873/fullhttps://doaj.org/toc/2297-055XObjective: 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.Xun WuDi WangKele QinChukwuemeka Daniel IroegbuKun XiangYuanjing ZhouQing GuanWeijie TangJun PengJianjun GuoJinfu YangJinfu YangChengming FanChengming FanChengming FanFrontiers Media S.A.articlemyocardial infarctionechocardiography-guidedintramyocardial injectionstem cellstherapyDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021) |
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myocardial infarction echocardiography-guided intramyocardial injection stem cells therapy Diseases of the circulatory (Cardiovascular) system RC666-701 |
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myocardial infarction echocardiography-guided intramyocardial injection stem cells therapy Diseases of the circulatory (Cardiovascular) system RC666-701 Xun Wu Di Wang Kele Qin Chukwuemeka Daniel Iroegbu Kun Xiang Yuanjing Zhou Qing Guan Weijie Tang Jun Peng Jianjun Guo Jinfu Yang Jinfu Yang Chengming Fan Chengming Fan Chengming Fan Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction |
description |
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. |
format |
article |
author |
Xun Wu Di Wang Kele Qin Chukwuemeka Daniel Iroegbu Kun Xiang Yuanjing Zhou Qing Guan Weijie Tang Jun Peng Jianjun Guo Jinfu Yang Jinfu Yang Chengming Fan Chengming Fan Chengming Fan |
author_facet |
Xun Wu Di Wang Kele Qin Chukwuemeka Daniel Iroegbu Kun Xiang Yuanjing Zhou Qing Guan Weijie Tang Jun Peng Jianjun Guo Jinfu Yang Jinfu Yang Chengming Fan Chengming Fan Chengming Fan |
author_sort |
Xun Wu |
title |
Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction |
title_short |
Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction |
title_full |
Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction |
title_fullStr |
Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction |
title_full_unstemmed |
Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction |
title_sort |
cardiac repair with echocardiography-guided multiple percutaneous left ventricular intramyocardial injection of hipsc-cms after myocardial infarction |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/e49537715dfc478986c915353aece4c8 |
work_keys_str_mv |
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