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

Cytotherapy. 2014 Jul;16(7):873-80. doi: 10.1016/j.jcyt.2014.02.014. Epub 2014 May 13.

Abstract

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.

Keywords: arrhythmia therapy; cell therapy; gene therapy; pacemaker.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adenoviridae / genetics
  • Arrhythmias, Cardiac / pathology
  • Arrhythmias, Cardiac / therapy*
  • Biological Clocks*
  • Cell- and Tissue-Based Therapy*
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Stem Cells / cytology