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Related Experiment Video

Updated: Jun 13, 2025

Generating Self-Assembling Human Heart Organoids Derived from Pluripotent Stem Cells
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Modeling the atrioventricular conduction axis using human pluripotent stem cell-derived cardiac assembloids.

Jiuru Li1, Alexandra Wiesinger1, Lianne Fokkert1

  • 1Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands.

Cell Stem Cell
|September 11, 2024
PubMed
Summary

Researchers developed novel AV canal cardiomyocytes (AVCMs) and cardiac assembloids to study heart rhythm disorders. This model revealed intracellular calcium mishandling as a cause of LMNA-associated AV conduction block.

Keywords:
LMNAassembloidatrioventricular nodeatrioventricular canalcardiomyocyteconductiondifferentiationelectrophysiologyheart diseaseiPSC

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Area of Science:

  • Cardiovascular Biology
  • Stem Cell Biology
  • Cardiac Electrophysiology

Background:

  • The atrioventricular (AV) conduction axis is crucial for sequential heart chamber contraction.
  • Dysfunction of AV nodal tissue leads to significant cardiac rhythm disturbances.
  • Existing human models for studying AV nodal function are limited.

Purpose of the Study:

  • To develop a reproducible method for generating AV canal cardiomyocytes (AVCMs) with in vivo-like characteristics.
  • To create functional human cardiac assembloids for studying AV conduction.
  • To investigate the cellular mechanisms underlying AV conduction block.

Main Methods:

  • Generated AV canal cardiomyocytes (AVCMs) using novel differentiation strategies.
  • Constructed cardiac assembloids comprising atrial, AVCM, and ventricular spheroids.
  • Utilized assembloids to analyze electrophysiological properties and intracellular calcium handling.

Main Results:

  • Reproducibly generated AVCMs exhibiting in vivo-like gene expression and electrophysiology.
  • Cardiac assembloids recapitulated unidirectional AV conduction and the "fast-slow-fast" activation pattern.
  • Identified intracellular calcium mishandling as the basis for LMNA-associated AV conduction block.

Conclusions:

  • Introduced innovative cell differentiation and tissue engineering strategies for AV conduction studies.
  • Developed a human cardiac assembloid model to investigate heart rhythm disorders.
  • Provided new insights into the mechanisms of LMNA-associated AV conduction block.