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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Main Authors: Xun Wu, Di Wang, Kele Qin, Chukwuemeka Daniel Iroegbu, Kun Xiang, Yuanjing Zhou, Qing Guan, Weijie Tang, Jun Peng, Jianjun Guo, Jinfu Yang, Chengming Fan
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2021.768873/full
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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
collection DOAJ
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.
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spelling doaj.art-e49537715dfc478986c915353aece4c82022-12-21T22:54:50ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-11-01810.3389/fcvm.2021.768873768873Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial InfarctionXun Wu0Di Wang1Kele Qin2Chukwuemeka Daniel Iroegbu3Kun Xiang4Yuanjing Zhou5Qing Guan6Weijie Tang7Jun Peng8Jianjun Guo9Jinfu Yang10Jinfu Yang11Chengming Fan12Chengming Fan13Chengming Fan14Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaHunan Provincial Key Laboratory of Cardiovascular Research, Changsha, ChinaDepartment of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaHunan Provincial Key Laboratory of Cardiovascular Research, Changsha, ChinaDepartment of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaHunan Provincial Key Laboratory of Cardiovascular Research, Changsha, ChinaHunan Fangsheng Pharmaceutical Co., Ltd., Changsha, ChinaDepartment of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaHunan Provincial Key Laboratory of Cardiovascular Research, Changsha, ChinaDepartment of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaHunan Provincial Key Laboratory of Cardiovascular Research, Changsha, ChinaHunan Fangsheng Pharmaceutical Co., Ltd., Changsha, ChinaObjective: 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.https://www.frontiersin.org/articles/10.3389/fcvm.2021.768873/fullmyocardial infarctionechocardiography-guidedintramyocardial injectionstem cellstherapy
spellingShingle 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
Frontiers in Cardiovascular Medicine
myocardial infarction
echocardiography-guided
intramyocardial injection
stem cells
therapy
title 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_short 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
topic myocardial infarction
echocardiography-guided
intramyocardial injection
stem cells
therapy
url https://www.frontiersin.org/articles/10.3389/fcvm.2021.768873/full
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