This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 100/8/1112    most recent 01.RES.0000265845.04439.78v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cho, H. C. Articles by Marbán, E. Search for Related Content PubMed PubMed Citation Articles by Cho, H. C. Articles by Marbán, E. Related Collections Pacemaker Arrythmias-basic studies

Creation of a Biological Pacemaker by Cell Fusion

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.

Correspondence to Eduardo Marbán, MD, PhD, Chief of Cardiology, 858 Ross Bldg, 720 Rutland Ave, Baltimore, MD 21205. 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 ß-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 I_f-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

This article has been cited by other articles:

				M. R. Rosen, P. R. Brink, I. S. Cohen, and R. B. Robinson Cardiac Pacing: From Biological to Electronic ... to Biological? Circ Arrhythmia Electrophysiol, April 1, 2008; 1(1): 54 - 61. [Abstract] [Full Text] [PDF]