Stem cell-based biological pacemakers from proof of principle to therapy: a review

Electronic pacemakers are the standard therapy for bradycardia-related symptoms but have shortcomings. Over the past 15 years, experimental evidence has demonstrated that gene and cell-based therapies can create a biological pacemaker. Recently, physiologically acceptable rates have been reported with an adenovirus-based approach. However, adenovirus-based protein expression does not last more than 4 weeks, which limits its clinical applicability. Cell-based platforms are potential candidates for longer expression. Currently there are two cell-based approaches being tested: (i) mesenchymal stem cells used as a suitcase for delivering pacemaker genes and (ii) pluripotent stem cells differentiated down a cardiac lineage with endogenous pacemaker activity. This review examines the current achievements in engineering a biological pacemaker, defines the patient population for whom this device would be useful and identifies the challenges still ahead before cell therapy can replace current electronic devices.