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Updated: May 7, 2026
Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection
Published on: February 17, 2015
Genetically-engineered mesenchymal stem cells transfected with human HCN1 gene to create cardiac pacemaker cells
Ya-Feng Zhou1, Xiang-Jun Yang, Hong-Xia Li
1Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Objective:
To test the proof-of-principle that genetically-engineered mesenchymal stem cells (MSCs) transfected with the human hyperpolarization-activated cyclic nucleotide-gated channel 1 (hHCN1) gene can be modified to become cardiac pacemaker cells.
Methods:
MSCs were transfected with the hHCN1 gene using lentiviral-based transfection. The expressed pacemaker current (I(f)) in hHCN1-transfected MSCs was recorded using whole-cell patch-clamp analysis. The effect of the hHCN1-transfected MSCs on cardiomyocyte excitability was determined by coculturing the MSCs with neonatal rabbit ventricular myocytes (NRVM). The spontaneous action potentials of the NRVM were recorded by whole-cell current-clamp analysis.
Results:
A high level time- and voltage-dependent inward hyperpolarization current that was inhibited by 4 mM caesium chloride was detected in hHCN1-transfected MSCs, suggesting that the HCN1 proteins acted as I(f) channels in MSCs. The mean ± SE beating frequency in NRVMs cocultured with control MSCs transfected with the pcDNA3 plasmid control was 82 ± 8 beats/min (n = 5) compared with 129 ± 11 beats/min (n = 5) in NRVMs cocultured with hHCN1-transfected MSCs.
Conclusions:
Genetically-engineered MSCs transfected with the hHCN1 gene can be modified to become cardiac pacemaker cells.
