Effects of different administration routes of chimeric antigen receptor T cells on arrhythmias in mice with myocardial infarction
10.12025/j.issn.1008-6358.2024.20240501
- VernacularTitle:嵌合抗原受体T细胞经不同给药途径对小鼠心肌梗死后心律失常的影响
- Author:
Yuanxin ZHANG
1
;
Puyuan YANG
2
;
Penghan FU
2
;
Xiangmeng KONG
1
;
Xuanming YANG
2
;
Qingyong ZHANG
1
Author Information
1. Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
2. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
- Publication Type:Originalarticle
- Keywords:
chimeric antigen receptor T;
myocardial infarction;
arrhythmias;
myocardial injection;
intravenous injection
- From:
Chinese Journal of Clinical Medicine
2024;31(4):612-618
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effect of chimeric antigen receptor (CAR) T cells on myocardial infarction (MI) and observe the impact of different administration routes on CAR-T cell cardiac toxicity. Methods Twenty-four SCID Beige immunodeficient mice, which successfully established a myocardial infarction model, were randomly divided into Hank’s balanced salt solution (HBSS) group, CAR-TIM group, CAR-TIV group, and CAR-TIMIV group (n＝6 for each group). In addition, a Sham group (n＝6) was set up. The Sham group, HBSS group, CAR-TIM group, and CAR-TIMIV group were injected with HBSS or CAR-T cells via intramyocardial injection on the 7th day after modeling. The Sham group, HBSS group, CAR-TIV group, and CAR-TIMIV group were injected with HBSS or CAR-T cells via tail vein injection on the 7th day and 14th day after modeling. After 28 days of modeling, the electrical physiological indicators of the mice were observed, and the myocardial tissues were subjected to Masson staining to calculate the area of myocardial infarction. Results Compared with the Sham group, the HBSS group had significant increases in myocardial infarction size and incidence of arrhythmia (P＜0.05). Compared with HBSS group, different routes of CAR-T cell therapy significantly reduced the area of myocardial infarction (all P＜0.05) and significantly increased the incidence of arrhythmia (all P＜0.05). There was no significant difference in the effect of CAR-TIV and CAR-TIM groups on the area of myocardial infarction and the incidence of arrhythmia. Compared with the CAR-TIV group,the area of myocardial infarction significantly reduced in the CAR-TIMIV group (P＜0.05), with no significant difference in the incidence of arrhythmia between the two groups. Conclusions Intravenous and local myocardial injection of CAR-T cells can effectively reduce the myocardial infarction area but increase the incidence of arrhythmia. The mechanism needs further study.
