Referenced in: none

Automatically associated channels: HCN1

Title: Genetically-engineered mesenchymal stem cells transfected with human HCN1 gene to create cardiac pacemaker cells.

Authors: Ya-Feng Zhou, Xiang-jun Yang, Hong-xia Li, Lian-Huan Han, Wen-ping Jiang

Journal, date & volume: J. Int. Med. Res., 2013 Oct , 41, 1570-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24097828

Abstract
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.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.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.Genetically-engineered MSCs transfected with the hHCN1 gene can be modified to become cardiac pacemaker cells.