Published online before print March 29, 2007, doi: 10.1161/01.RES.0000265845.04439.78
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Submitted on February 14, 2007
Revised on March 14, 2007
Accepted on March 21, 2007
Creation of a Biological Pacemaker by Cell Fusion
Hee Cheol Cho ;
From the Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD. Present address for H.C.C.: Excigen Inc, Baltimore, Md. Present address for Y.K.: Okayama Innovation Center for Nanobio-targeted Therapy, School of Medicine, Okayama University, Japan.
* To whom correspondence should be addressed. E-mail: marban{at}jhmi.edu.
As an alternative to electronic pacemakers, we explored the feasibility of converting ventricular myocytes into pacemakers by somatic cell fusion. The idea is to create chemically induced fusion between myocytes and syngeneic fibroblasts engineered to express HCN1 pacemaker channels (HCN1-fibroblasts). HCN1-fibroblasts were fused with freshly isolated guinea pig ventricular myocytes using polyethylene-glycol 1500. In vivo fused myocyte-HCN1-fibroblast cells exhibited spontaneously oscillating action potentials; the firing frequency increased with 
-adrenergic stimulation. The heterokaryons created ectopic ventricular pacemaker activity in vivo at the site of cell injection. Coculture of nonfused HCN1-fibroblasts and myocytes without polyethylene-glycol 1500 revealed no evidence of dye transfer, demonstrating that the If-mediated pacemaker activity arises from heterokaryons rather than electrotonic coupling. This nonviral, non-stem cell approach enables autologous, adult somatic cell therapy to create biopacemakers.
Key words: arrhythmia • biological pacemaker • cell fusion • cell transplantation • heart rate • ion channels • pacemaker
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