Image_1_Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction.TIF
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.
History
References
- https://doi.org//10.1016/j.jacc.2017.04.052
- https://doi.org//10.1093/eurheartj/ehx343
- https://doi.org//10.1016/j.tcm.2014.08.004
- https://doi.org//10.1016/j.jacc.2015.04.039
- https://doi.org//10.3389/fcvm.2017.00047
- https://doi.org//10.1016/j.cell.2007.11.019
- https://doi.org//10.1001/jamacardio.2016.2750
- https://doi.org//10.1113/jp273098
- https://doi.org//10.1006/jmcc.2001.1367
- https://doi.org//10.1002/stem.1571
- https://doi.org//10.1016/j.jtcvs.2007.07.071
- https://doi.org//10.1093/cvr/cvy207
- https://doi.org//10.1016/j.yjmcc.2019.09.011
- https://doi.org//10.1038/nbt1327
- https://doi.org//10.1126/scitranslmed.aax2992
- https://doi.org//10.1016/j.yjmcc.2020.03.003
- https://doi.org//10.1007/s12265-018-9801-5
- https://doi.org//10.1155/2018/1909346
- https://doi.org//10.1038/nbt0907-993
- https://doi.org//10.1161/CIRCRESAHA.117.310710
- https://doi.org//10.3389/fcell.2020.00036
- https://doi.org//10.1007/s00395-017-0606-5
- https://doi.org//10.7150/thno.56757
- https://doi.org//10.1093/cvr/cvaa215
- https://doi.org//10.1371/journal.pone.0245571
- https://doi.org//10.1161/CIRCRESAHA.116.308937
- https://doi.org//10.1161/CIRCRESAHA.118.313251
- https://doi.org//10.1002/ccd.1164
- https://doi.org//10.1016/j.jacc.2007.07.054
- https://doi.org//10.1016/j.scr.2007.06.001
- https://doi.org//10.1016/j.ijbiomac.2018.02.111
- https://doi.org//10.1016/j.jstrokecerebrovasdis.2016.12.021
- https://doi.org//10.1161/CIRCULATIONAHA.111.076950
- https://doi.org//10.3109/15376516.2012.666650
CC BY 4.0