An iPS-derived in vitro model of human atrial conduction

Sherri M. Biendarra-Tiegs, Sergey Yechikov, Bhupinder Shergill, Brittany Brumback, Kentaro Takahashi, Venktesh S. Shirure, Ruth Estelle Gonzalez, Laura Houshmand, Denise Zhong, Kuo Chan Weng, Jon Silva, Timothy W. Smith, Stacey L. Rentschler, Steven C. George

Research output: Contribution to journalArticlepeer-review

Abstract

Atrial fibrillation (AF) is the most common arrhythmia in the United States, affecting approximately 1 in 10 adults, and its prevalence is expected to rise as the population ages. Treatment options for AF are limited; moreover, the development of new treatments is hindered by limited (1) knowledge regarding human atrial electrophysiological endpoints (e.g., conduction velocity [CV]) and (2) accurate experimental models. Here, we measured the CV and refractory period, and subsequently calculated the conduction wavelength, in vivo (four subjects with AF and four controls), and ex vivo (atrial slices from human hearts). Then, we created an in vitro model of human atrial conduction using induced pluripotent stem (iPS) cells. This model consisted of iPS-derived human atrial cardiomyocytes plated onto a micropatterned linear 1D spiral design of Matrigel. The CV (34–41 cm/s) of the in vitro model was nearly five times faster than 2D controls (7–9 cm/s) and similar to in vivo (40–64 cm/s) and ex vivo (28–51 cm/s) measurements. Our iPS-derived in vitro model recapitulates key features of in vivo atrial conduction and may be a useful methodology to enhance our understanding of AF and model patient-specific disease.

Original languageEnglish
Article numbere15407
JournalPhysiological Reports
Volume10
Issue number18
DOIs
StatePublished - Sep 2022

Keywords

  • atrial fibrillation
  • conduction velocity
  • ex vivo
  • in vivo
  • refractory period
  • wavelength

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