Mesenchymal stem cells as a gene delivery system to create biological pacemaker cells in vitro.
Pacemaker cells differ from common cardiomyocytes due to the presence of a spontaneous depolarization process during the diastolic phase of the cardiac cycle. This is due to hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are responsible for providing an inward current. Genetically engineered mesenchymal stem cells (MSCs) were transfected with hHCN4 genes using lentiviral transfection, and their potential use as biological pacemaker cells was investigated. In addition to expressing an anticipated high level of the hHCN4 gene, MSCs transfected with hHCN4 genes also expressed characteristic hHCN4 protein, a cardiac pacemaker-like current and were capable of increasing the spontaneous beating rate of co-cultured cardiac myocytes. Control MSCs did not exert these effects. It is hypothesized that genetically engineered MSCs transfected with hHCN4 genes by lentiviral transfection can be modified to be cardiac pacemaker cells in vitro.
Yang
X-J
XJ
Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
Zhou
Y-F
YF
Li
H-X
HX
Han
L-H
LH
Jiang
W-P
WP
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D018920:Coculture Techniques; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D011817:Rabbits; D023822:Tissue Engineering
D054815:Cyclic Nucleotide-Gated Cation Channels; C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009124:Muscle Proteins; D015221:Potassium Channels