Biological pacemakers as a therapy for cardiac arrhythmias.
OBJECTIVE
Cardiac rhythm disorders are caused by malfunctions of impulse generation or conduction. Malfunctions of impulse generation, that is, defects in pacemaking, are often life-threatening. Present therapies span a wide array of approaches, but remain largely palliative. Recent progress in understanding of the underlying biology of pacemaking opens up new prospects for better alternatives to the present routine. Specifically, development and use of biological pacemakers could prove to be advantageous to the conventional approaches.


RESULTS
We review the current state of the art in gene and cell-based approaches to correct cardiac rhythm disturbances. These include genetic suppression of an ionic current, embryonic as well as adult stem cell therapies, novel synthetic pacemaker channels, and adult somatic cell-fusion approach.


CONCLUSIONS
Biological pacemaking can be achieved by modulating ionic currents by gene transfer or by delivering engineered pacemaker cells into normally quiescent myocardium. The present state of development is proof-of-concept; we are now working on reducing to practice a stable, reliable biological product as an alternative to electronic pacemakers.
Marbán
Eduardo
E
Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. eduardo.marban@csmc.edu
Cho
Hee Cheol
HC
D053687:Adult Stem Cells; D001145:Arrhythmias, Cardiac / Q000628:therapy*; D001683:Biological Clocks; D002459:Cell Fusion; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics; D053595:Embryonic Stem Cells; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors
D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying