Reconstructing the heart using iPSCs: Engineering strategies and applications

J Mol Cell Cardiol. 2021 Aug:157:56-65. doi: 10.1016/j.yjmcc.2021.04.006. Epub 2021 Apr 22.

Abstract

Induced pluripotent stem cells (iPSCs) have emerged as a key component of cardiac tissue engineering, enabling studies of cardiovascular disease mechanisms, drug responses, and developmental processes in human 3D tissue models assembled from isogenic cells. Since the very first engineered heart tissues were introduced more than two decades ago, a wide array of iPSC-derived cardiac spheroids, organoids, and heart-on-a-chip models have been developed incorporating the latest available technologies and materials. In this review, we will first outline the fundamental biological building blocks required to form a functional unit of cardiac muscle, including iPSC-derived cells differentiated by soluble factors (e.g., small molecules), extracellular matrix scaffolds, and exogenous biophysical maturation cues. We will then summarize the different fabrication approaches and strategies employed to reconstruct the heart in vitro at varying scales and geometries. Finally, we will discuss how these platforms, with continued improvements in scalability and tissue maturity, can contribute to both basic cardiovascular research and clinical applications in the future.

Keywords: 3D bioprinting; Cardiac organoids; Cardiovascular tissue engineering; Engineered heart tissue; iPSC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Biocompatible Materials
  • Biomarkers
  • Cell Culture Techniques
  • Cell Differentiation*
  • Drug Development
  • Drug Discovery
  • Gene Expression Regulation, Developmental
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism*
  • Myocardium / cytology*
  • Myocardium / metabolism*
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism*
  • Regeneration*
  • Tissue Culture Techniques
  • Tissue Engineering / methods
  • Tissue Scaffolds

Substances

  • Biocompatible Materials
  • Biomarkers