Engineered models of the human heart: Directions and challenges

Stem Cell Reports. 2021 Sep 14;16(9):2049-2057. doi: 10.1016/j.stemcr.2020.11.013. Epub 2020 Dec 18.

Abstract

Human heart (patho)physiology is now widely studied using human pluripotent stem cells, but the immaturity of derivative cardiomyocytes has largely limited disease modeling to conditions associated with mutations in cardiac ion channel genes. Recent advances in tissue engineering and organoids have, however, created new opportunities to study diseases beyond "channelopathies." These synthetic cardiac structures allow quantitative measurement of contraction, force, and other biophysical parameters in three-dimensional configurations, in which the cardiomyocytes in addition become more mature. Multiple cardiac-relevant cell types are also often combined to form organized cardiac tissue mimetic constructs, where cell-cell, cell-extracellular matrix, and paracrine interactions can be mimicked. In this review, we provide an overview of some of the most promising technologies being implemented specifically in personalized heart-on-a-chip models and explore their applications, drawbacks, and potential for future development.

Keywords: cardiovascular disease modeling; engineered heart tissue; force of contraction; heart-on-a-chip; human pluripotent stem cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Culture Techniques
  • Heart / physiology*
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Lab-On-A-Chip Devices
  • Myocardium / metabolism*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Tissue Engineering / methods*
  • Tissue Engineering / trends*