Implementing Biological Pacemakers: Design Criteria for Successful Transition From Concept to Clinic

Elizabeth R. Komosa, David W. Wolfson, Michael Bressan, Hee Cheol Cho, Brenda M. Ogle

Research output: Contribution to journalReview articlepeer-review


Each heartbeat that pumps blood throughout the body is initiated by an electrical impulse generated in the sinoatrial node (SAN). However, a number of disease conditions can hamper the ability of the SAN′s pacemaker cells to generate consistent action potentials and maintain an orderly conduction path, leading to arrhythmias. For symptomatic patients, current treatments rely on implantation of an electronic pacing device. However, complications inherent to the indwelling hardware give pause to categorical use of device therapy for a subset of populations, including pediatric patients or those with temporary pacing needs. Cellular-based biological pacemakers, derived in vitro or in situ, could function as a therapeutic alternative to current electronic pacemakers. Understanding how biological pacemakers measure up to the SAN would facilitate defining and demonstrating its advantages over current treatments. In this review, we discuss recent approaches to creating biological pacemakers and delineate design criteria to guide future progress based on insights from basic biology of the SAN. We emphasize the need for long-term efficacy in vivo via maintenance of relevant proteins, source-sink balance, a niche reflective of the native SAN microenvironment, and chronotropic competence. With a focus on such criteria, combined with delivery methods tailored for disease indications, clinical implementation will be attainable.

Original languageEnglish (US)
Pages (from-to)E009957
JournalCirculation: Arrhythmia and Electrophysiology
Issue number10
StatePublished - Oct 1 2021
Externally publishedYes


  • cell differentiation
  • cellular reprogramming
  • heart rate
  • pacemaker, artificial
  • sinoatrial node
  • stem cell niche

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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