Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?
Normal rhythms originate in the sino-atrial node, a specialized cardiac tissue consisting of only a few thousands of nodal pacemaker cells. Malfunction of pacemaker cells due to diseases or aging leads to rhythm generation disorders (for example, bradycardias and sick-sinus syndrome (SSS)), which often necessitate the implantation of electronic pacemakers. Although effective, electronic devices are associated with such shortcomings as limited battery life, permanent implantation of leads, lead dislodging, the lack of autonomic responses and so on. Here, various gene- and cell-based approaches, with a particular emphasis placed on the use of pluripotent stem cells and the hyperpolarization-activated cyclic nucleotide-gated-encoded pacemaker gene family, that have been pursued in the past decade to reconstruct bio-artificial pacemakers as alternatives will be discussed in relation to the basic biological insights and translational regenerative potential.
Center of Cardiovascular Research, Mount Sinai School of Medicine, New York, NY 10029, USA. ronald.li@mssm.edu
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D001145:Arrhythmias, Cardiac / Q000628:therapy; D001683:Biological Clocks / Q000502:physiology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D010138:Pacemaker, Artificial; D039904:Pluripotent Stem Cells / Q000637:transplantation*; D015221:Potassium Channels / Q000235:genetics*
D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels