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Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity
Published on: July 10, 2019
Management of engraftment arrhythmias associated with human-induced pluripotent stem cell-derived cardiomyocytes
Aixue Zhang1, Yufan Liu1, Yanwei Wei1
1TEDA International Cardiovascular Hospital, Tianjin University, Tianjin, China.
Insights
High-dose human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) transplantation increases the risk of early afterdepolarizations (EAs). Lower doses may mitigate EA occurrence, suggesting dose-dependent safety concerns for cell therapy in myocardial infarction.
Area of Science:
- Cardiovascular Medicine
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Intramyocardial injection of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) shows promise for myocardial infarction treatment.
- Early afterdepolarizations (EAs) occurring post-transplantation pose a significant barrier to the clinical translation of this cell therapy.
Purpose of the Study:
- To characterize the nature of EAs following hiPSC-CM transplantation.
- To identify critical risk factors associated with the development of EAs after hiPSC-CM transplantation.
Main Methods:
- Patients undergoing coronary artery bypass grafting (CABG) with hiPSC-CM transplantation (experimental) or isolated CABG (control) were studied.
- Experimental group patients received low (0.5×10^8) or high (1.5×10^8) doses of hiPSC-CMs.
- EA characteristics were analyzed, and univariate logistic regression identified risk factors for EAs.
Main Results:
- EAs occurred in 54.2% of hiPSC-CM recipients, originating from the injection site.
- EAs progressed from paroxysmal to sustained episodes with increased heart rate and R-R variability.
- Higher hiPSC-CM dose significantly correlated with increased EA incidence (83.3% high-dose vs. 25.0% low-dose; P=0.012).
Conclusions:
- Early afterdepolarizations following hiPSC-CM transplantation appear to be driven by an automaticity mechanism.
- The dosage of hiPSC-CMs is a significant factor influencing the incidence of EAs, highlighting a dose-dependent risk.
Background:
Intramyocardial injection of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is a promising cell replacement therapy for myocardial infarction, but engraftment arrhythmias (EAs) posttransplantation hinder their clinical translation.
Objective:
This study aims to analyze EA characteristics after hiPSC-CM transplantation and to identify risk factors associated with the occurrence of EAs.
Methods:
This study included patients undergoing coronary artery bypass grafting (CABG) combined with hiPSC-CM transplantation (experimental group) or isolated CABG (control group) at our hospital between November 2023 and November 2025. Patients in the experimental group were assigned to low- and high-dose groups (0.5 × 108 and 1.5 × 108 cells). EA characteristics were analyzed and compared between the 2 subgroups. Univariate logistic regression was performed to identify risk factors for EAs.
Results:
A total of 24 patients in the experimental group were enrolled, 13 (54.2%) of whom developed EAs originating from the cell injection site (localized by electrocardiogram QRS morphology). Initially, EAs were paroxysmal (heart rate: 55-96 bpm, 72.15 ± 9.77 bpm), progressing to sustained episodes over hours with increased heart rate (max 111-185 bpm, 146.00 ± 21.02 bpm) and R-R interval variability. No hemodynamic abnormalities were detected in any patient during EA episodes. Atrial pacing and electrical cardioversion reduced EA rate but failed to terminate EAs. EA incidence was significantly higher in the high-dose than low-dose group (10/12 [83.3%] vs 3/12 [25.0%], P = .012). Univariate logistic regression showed hiPSC-CM dose was significantly associated with EA occurrence (odds ratio, 15.00; 95% confidence interval, 2.02-111.17; P = .008).
Conclusion:
The occurrence of EAs was likely driven by an automaticity mechanism, and hiPSC-CM transplantation dose was significantly correlated with EA incidence.
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