Cellular Reprogramming Approaches to Engineer Cardiac Pacemakers

Curr Cardiol Rep. 2020 Mar 30;22(5):29. doi: 10.1007/s11886-020-01281-6.

Abstract

Purpose of review: The goal of this paper is to review present knowledge regarding biological pacemakers created by somatic reprogramming as a platform for mechanistic and metabolic understanding of the rare subpopulation of pacemaker cells, with the ultimate goal of creating biological alternatives to electronic pacing devices.

Recent findings: Somatic reprogramming of cardiomyocytes by reexpression of embryonic transcription factor T-box 18 (TBX18) converts them into pacemaker-like. Recent studies take advantage of this model to gain insight into the electromechanical, metabolic, and architectural intricacies of the cardiac pacemaker cell across various models, including a surgical model of complete atrioventricular block (CAVB) in adult rats. The studies reviewed here reinforce the potential utility of TBX18-induced pacemaker myocytes (iPMS) as a minimally invasive treatment for heart block. Several challenges which must be overcome to develop a viable therapeutic intervention based on these observations are discussed.

Keywords: Atrioventricular block; Biological pacemaker; Bradycardia; Gene therapy; Induced pacemaker myocytes.

Publication types

  • Review

MeSH terms

  • Animals
  • Atrioventricular Block
  • Cardiac Pacing, Artificial
  • Cellular Reprogramming*
  • Humans
  • Myocytes, Cardiac
  • Pacemaker, Artificial*
  • Rats
  • T-Box Domain Proteins

Substances

  • T-Box Domain Proteins